{"gene":"NUP42","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":1999,"finding":"The yeast FG-nucleoporin Rip1p (the S. cerevisiae ortholog of hCG1/NUP42) physically interacts with the C-terminal domain of the mRNA export factor Gle1p and with the DEAD-box protein Rat8p/Dbp5p on the cytoplasmic fibrils of the NPC. High-copy expression of Rip1p suppresses a GLE1 mutant. Rip1p contributes to the association of Gle1p with the pore, which in turn provides a binding site for Rat8p/Dbp5p, placing these factors in a terminal step of mRNA export. A human functional homologue of Rip1p, hCG1, rescues rip1Δ function in yeast, demonstrating evolutionary conservation.","method":"Genetic suppressor screen (high-copy suppression of gle1 mutant), co-immunoprecipitation, immunoelectron microscopy localization, yeast complementation assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — reciprocal genetic and biochemical approaches replicated across multiple methods in same study, with cross-species complementation confirming conservation","pmids":["10610322"],"is_preprint":false},{"year":2002,"finding":"HIV-1 Vpr docks at the nuclear envelope by interacting with the human nucleoporin hCG1 (NUP42). This interaction was identified by yeast two-hybrid, confirmed in vitro and in transfected cells. The interaction involves the N-terminal region of hCG1, not its FG-repeat domain. Using a nuclear import assay in digitonin-permeabilized cells, hCG1 was shown to participate in docking Vpr at the nuclear envelope.","method":"Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation in transfected cells, digitonin-permeabilized cell nuclear import assay, FRAP/photobleaching in live cells","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (Y2H, in vitro, cellular co-IP, functional import assay) in single study with rigorous controls","pmids":["12228227"],"is_preprint":false},{"year":2005,"finding":"The unique C-terminal 43 amino acid region of the hGle1B isoform binds specifically to the C-terminal non-FG region of hCG1 (NUP42). hNup155, hGle1B, and hCG1 form a heterotrimeric complex in vitro. siRNA-mediated depletion of hCG1 causes hGle1 accumulation in cytoplasmic foci and inhibits heat shock-induced Hsp70 mRNA export and Hsp70 protein production in HeLa cells, closely paralleling the role of the yeast ortholog Nup42/Rip1.","method":"Co-immunoprecipitation, in vitro complex reconstitution (heterotrimeric complex), siRNA knockdown, mRNA export assay (Hsp70 mRNA FISH), protein level analysis by immunoblot","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — in vitro complex reconstitution plus siRNA loss-of-function with specific export phenotype, corroborated by yeast ortholog function","pmids":["16000379"],"is_preprint":false},{"year":2012,"finding":"The nucleoporin-like protein NLP1 (hCG1/NUP42) localizes to the nuclear envelope and promotes CRM1-dependent nuclear protein export. NLP1 facilitates formation of trimeric complexes containing CRM1, RanGTP, and NES-containing cargo. These complexes can be dissociated by RanBP1 and/or Nup214. The FG repeats of NLP1 are not required for CRM1 binding. Overexpression of NLP1 enhances CRM1-dependent cargo export, while siRNA depletion reduces export rates.","method":"Immunofluorescence localization, co-immunoprecipitation, siRNA knockdown with nuclear export assay, overexpression with export assay, domain deletion mutagenesis","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — reciprocal gain- and loss-of-function experiments with defined export phenotype, domain mutagenesis, and protein complex characterization","pmids":["22250199"],"is_preprint":false},{"year":2017,"finding":"Nup42 is required for Gle1-mediated activation of the DEAD-box ATPase Dbp5 (hDDX19B) during mRNA export. The Nup42 carboxy-terminal domain (CTD) binds Gle1/hGle1B at a site distinct from the Gle1-Dbp5/DDX19B interaction interface, and a trimeric Nup42-CTD/Gle1-CTD/Dbp5 complex forms in the presence of IP6. Deletion of NUP42 abrogates the Gle1-Dbp5 interaction. In vitro, Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5 and DDX19B in a nonadditive manner, indicating they act through a shared mechanism. Disruption of Nup42 or IP6 binding interfaces on Gle1/hGle1B impairs mRNA export in both S. cerevisiae and human cells. This mechanism is completely conserved between yeast and humans.","method":"In vitro ATPase stimulation assay (reconstitution with recombinant proteins), co-immunoprecipitation, yeast genetic deletion and structure-function analysis, siRNA/overexpression in human cells, mRNA export assay, domain mutagenesis","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 1 — in vitro reconstitution of trimeric complex and ATPase activation, combined with genetic loss-of-function and domain mutagenesis across two species","pmids":["28869701"],"is_preprint":false},{"year":2026,"finding":"Nup42 is the strongest suppressor of heat-induced mRNA condensation identified in a whole-genome CRISPRi screen. Loss of Nup42 causes temperature- and transcription-dependent nuclear condensation of chaperone mRNAs (e.g., HSP70); these mRNAs are exported but remain translationally incompetent, leading to impaired chaperone production and thermosensitivity. Co-transcriptional mRNP packaging is a critical determinant of condensation in the absence of Nup42, revealing a nuclear, translation-independent layer of mRNP solubility control that selectively enables heat shock gene expression.","method":"Whole-genome CRISPRi screen (FRep-Seq platform), mRNA fractionation, live-cell imaging, translation assay, thermosensitivity phenotyping, transcription inhibition experiments","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 — genome-wide screen plus multiple orthogonal functional readouts, but preprint not yet peer-reviewed","pmids":["41727045"],"is_preprint":true}],"current_model":"NUP42 (hCG1/Rip1p) is an FG-nucleoporin located on the cytoplasmic face of the nuclear pore complex that acts as a scaffold to anchor the mRNA export factor Gle1/hGle1B at the NPC, where Gle1 and IP6 together activate the DEAD-box ATPase Dbp5/DDX19B to remodel mRNPs during mRNA export; additionally, NUP42 promotes CRM1-dependent protein export, docks HIV-1 Vpr at the nuclear envelope via the N-terminal region of hCG1, and safeguards heat-induced chaperone mRNAs from nuclear condensation to enable their translation during heat shock."},"narrative":{"teleology":[{"year":1999,"claim":"Establishing that Nup42/Rip1p physically links Gle1p and Dbp5p at the cytoplasmic face of the NPC answered how these mRNA export factors are recruited to the terminal export step, and cross-species complementation by human hCG1 demonstrated evolutionary conservation.","evidence":"Genetic suppressor screen, co-immunoprecipitation, immuno-EM, and yeast complementation in S. cerevisiae and human cells","pmids":["10610322"],"confidence":"High","gaps":["Biochemical mechanism by which Nup42 potentiates Dbp5 ATPase activity was not determined","Direct binding interfaces on Nup42 for Gle1 versus Dbp5 were not mapped","Bulk versus transcript-specific mRNA export contribution was unclear"]},{"year":2002,"claim":"Identification of hCG1/NUP42 as the nuclear envelope docking factor for HIV-1 Vpr revealed an unexpected viral exploitation of this nucleoporin, mapping the interaction to the N-terminal non-FG region.","evidence":"Yeast two-hybrid, in vitro binding, co-IP in transfected cells, and digitonin-permeabilized cell import assay","pmids":["12228227"],"confidence":"High","gaps":["Whether Vpr docking through Nup42 contributes to viral nuclear import or NPC disruption was not resolved","Structural basis of the Vpr–hCG1 interaction was not determined"]},{"year":2005,"claim":"Demonstrating that the hGle1B C-terminal tail binds the non-FG region of hCG1 and that their depletion blocks heat-shock Hsp70 mRNA export established that the yeast Nup42–Gle1 export axis is functionally conserved in human cells with transcript-selective consequences.","evidence":"In vitro reconstitution of hNup155–hGle1B–hCG1 heterotrimer, siRNA knockdown in HeLa cells, Hsp70 mRNA FISH, and immunoblot","pmids":["16000379"],"confidence":"High","gaps":["Whether Nup42 loss affects bulk poly(A)+ mRNA export or only specific transcripts was not fully resolved","Role of hNup155 within the trimeric complex was not functionally dissected"]},{"year":2012,"claim":"Discovery that NUP42/NLP1 promotes CRM1-dependent protein export independently of its FG repeats broadened Nup42 function beyond mRNA export and identified it as a facilitator of CRM1–RanGTP–NES-cargo complex assembly.","evidence":"Gain- and loss-of-function experiments (overexpression and siRNA), domain deletion mutagenesis, co-IP with CRM1 complexes, and nuclear export assays","pmids":["22250199"],"confidence":"High","gaps":["Whether the mRNA export and CRM1-dependent protein export functions are mechanistically coupled or independent was not tested","Structural basis of CRM1 binding to the non-FG region of Nup42 was not defined"]},{"year":2017,"claim":"Biochemical reconstitution of the Nup42-CTD/Gle1/Dbp5 trimeric complex with IP6 resolved the long-standing question of how Nup42 potentiates Gle1-mediated activation of Dbp5/DDX19B ATPase activity, showing Nup42 and IP6 act through a shared, non-additive mechanism conserved from yeast to humans.","evidence":"In vitro ATPase stimulation with recombinant proteins, co-IP, domain mutagenesis, yeast genetics, siRNA in human cells, and mRNA export assays across two species","pmids":["28869701"],"confidence":"High","gaps":["Atomic-resolution structure of the full Nup42-CTD/Gle1/Dbp5/IP6 complex was not available","Whether Nup42-mediated Dbp5 activation is transcript-selective was not addressed"]},{"year":2026,"claim":"A genome-wide CRISPRi screen identified Nup42 as the top suppressor of heat-induced mRNA condensation, revealing that beyond mRNA export, Nup42 safeguards co-transcriptional mRNP solubility of chaperone transcripts to enable their translation during heat shock. (preprint)","evidence":"CRISPRi screen (FRep-Seq), mRNA fractionation, live-cell imaging, translation assays, and transcription inhibition experiments (preprint)","pmids":["41727045"],"confidence":"Medium","gaps":["Findings await peer review","Direct molecular mechanism by which Nup42 prevents mRNA condensation (e.g., through mRNP remodeling or chaperoning) is unknown","Whether this mRNP solubility function operates through the Gle1–Dbp5 axis or an independent pathway was not determined"]},{"year":null,"claim":"A unifying structural and mechanistic model explaining how Nup42 coordinates its dual roles in mRNA export (Gle1/Dbp5 activation), CRM1-dependent protein export, viral docking, and mRNP solubility control remains to be established.","evidence":"","pmids":[],"confidence":"Low","gaps":["No high-resolution structure of full-length Nup42 in complex with its partners exists","Whether the mRNA export, CRM1 export, and mRNP solubility functions compete for the same Nup42 pools or operate through distinct sub-complexes is unknown","In vivo contribution of Nup42 to bulk versus heat-shock-specific mRNA export in mammalian tissues has not been assessed"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,4]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,1,2,3]}],"pathway":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,4]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3,4]}],"complexes":["Nuclear pore complex (NPC)","Nup42/Gle1/Dbp5 trimeric complex","hNup155/hGle1B/hCG1 heterotrimer"],"partners":["GLE1","DBP5","DDX19B","NUP155","XPO1","NUP214"],"other_free_text":[]},"mechanistic_narrative":"NUP42 (hCG1/Rip1p) is an FG-nucleoporin on the cytoplasmic face of the nuclear pore complex that serves as a scaffold anchoring the mRNA export factor Gle1/hGle1B at the NPC, where the Nup42 C-terminal domain, Gle1, and inositol hexakisphosphate cooperatively stimulate the DEAD-box ATPase Dbp5/DDX19B to remodel mRNPs during the terminal step of mRNA export [PMID:10610322, PMID:28869701]. Nup42 forms a heterotrimeric complex with hNup155 and hGle1B, and its depletion causes cytoplasmic mislocalization of Gle1 and specifically impairs heat-shock-induced Hsp70 mRNA export and chaperone protein production [PMID:16000379]. Independent of its mRNA export role, Nup42 promotes CRM1-dependent nuclear protein export by facilitating trimeric CRM1–RanGTP–NES-cargo complex formation through a mechanism that does not require its FG repeats [PMID:22250199]. The N-terminal region of Nup42 also serves as a docking site for HIV-1 Vpr at the nuclear envelope [PMID:12228227]."},"prefetch_data":{"uniprot":{"accession":"O15504","full_name":"Nucleoporin NUP42","aliases":["NLP-1","NUP42 homolog","Nucleoporin hCG1","Nucleoporin-42","Nucleoporin-like protein 2"],"length_aa":423,"mass_kda":44.9,"function":"Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm (Microbial infection) In case of infection by HIV-1, it may participate in the docking of viral Vpr at the nuclear envelope","subcellular_location":"Nucleus, nuclear pore complex; Nucleus membrane","url":"https://www.uniprot.org/uniprotkb/O15504/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP42","classification":"Not Classified","n_dependent_lines":49,"n_total_lines":1208,"dependency_fraction":0.04056291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NCL","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2},{"gene":"SNRPA","stoichiometry":0.2},{"gene":"SNRPF","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP42","total_profiled":1310},"omim":[{"mim_id":"619998","title":"NUCLEOPORIN 42; NUP42","url":"https://www.omim.org/entry/619998"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear membrane","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP42"},"hgnc":{"alias_symbol":["NLP_1","CG1","hCG1","H_RG271G13.9"],"prev_symbol":["NUPL2"]},"alphafold":{"accession":"O15504","domains":[{"cath_id":"-","chopping":"110-208","consensus_level":"high","plddt":79.3231,"start":110,"end":208},{"cath_id":"-","chopping":"391-421","consensus_level":"high","plddt":81.8639,"start":391,"end":421}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15504","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15504-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15504-F1-predicted_aligned_error_v6.png","plddt_mean":55.34},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP42","jax_strain_url":"https://www.jax.org/strain/search?query=NUP42"},"sequence":{"accession":"O15504","fasta_url":"https://rest.uniprot.org/uniprotkb/O15504.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15504/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15504"}},"corpus_meta":[{"pmid":"12228227","id":"PMC_12228227","title":"Docking 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cell","url":"https://pubmed.ncbi.nlm.nih.gov/25544563","citation_count":173,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32807901","id":"PMC_32807901","title":"UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.","date":"2020","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/32807901","citation_count":168,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"20936779","id":"PMC_20936779","title":"A human MAP kinase interactome.","date":"2010","source":"Nature methods","url":"https://pubmed.ncbi.nlm.nih.gov/20936779","citation_count":165,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"9621063","id":"PMC_9621063","title":"Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex.","date":"1998","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/9621063","citation_count":160,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"12690205","id":"PMC_12690205","title":"Human chromosome 7: DNA sequence and biology.","date":"2003","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/12690205","citation_count":154,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"18461144","id":"PMC_18461144","title":"Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance.","date":"2008","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/18461144","citation_count":148,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"32344865","id":"PMC_32344865","title":"Comparative Application of BioID and TurboID for Protein-Proximity Biotinylation.","date":"2020","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/32344865","citation_count":146,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"31871319","id":"PMC_31871319","title":"Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms.","date":"2019","source":"Nature cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/31871319","citation_count":137,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"10610322","id":"PMC_10610322","title":"The RNA export factor Gle1p is located on the cytoplasmic fibrils of the NPC and physically interacts with the FG-nucleoporin Rip1p, the DEAD-box protein Rat8p/Dbp5p and a new protein Ymr 255p.","date":"1999","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/10610322","citation_count":134,"is_preprint":false,"source_track":"gene2pubmed"},{"pmid":"10601273","id":"PMC_10601273","title":"Nuclear import of hepatic glucokinase depends upon glucokinase regulatory protein, whereas export is due to a nuclear export signal sequence in glucokinase.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10601273","citation_count":115,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9503,"output_tokens":1530,"usd":0.025729},"stage2":{"model":"claude-opus-4-6","input_tokens":4747,"output_tokens":2016,"usd":0.111202},"total_usd":0.324047,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":21029,"output_tokens":3491,"usd":0.057726},"round2_rules_fired":"R3","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5662,"output_tokens":2318,"usd":0.12939}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"The unique C-terminal 43 amino acid region of hGle1B isoform binds the C-terminal non-FG region of hCG1/NUP42, and hNup155, hGle1B, and hCG1 form a heterotrimeric complex in vitro; siRNA-mediated depletion of hCG1 causes hGle1 accumulation in cytoplasmic foci and inhibits Hsp70 mRNA export, demonstrating hCG1 is required for NPC localization of hGle1 and mRNA export.\",\n      \"method\": \"In vitro binding assays, siRNA knockdown, co-immunoprecipitation, fluorescence microscopy\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (in vitro complex reconstitution, siRNA, localization, functional mRNA export assay), Moderate evidence\",\n      \"pmids\": [\"16000379\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"HIV-1 Vpr interacts with the human nucleoporin hCG1/NUP42 via the N-terminal region of hCG1 (not the FG repeat domain), and this interaction mediates docking of Vpr at the nuclear envelope; hCG1 participates in the nuclear import step of Vpr as demonstrated by nuclear import assays in digitonin-permeabilized cells.\",\n      \"method\": \"Yeast two-hybrid, in vitro binding, co-immunoprecipitation in transfected cells, FRAP, nuclear import assay in digitonin-permeabilized cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Y2H, in vitro, co-IP, functional import assay), Moderate evidence\",\n      \"pmids\": [\"12228227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"NLP1/hCG1/NUP42 localizes to the nuclear envelope and nucleus, promotes formation of CRM1-RanGTP export complexes (with or without NES cargo), and functions as an accessory factor in CRM1-dependent nuclear protein export; the FG repeats of NLP1 are not the primary CRM1-binding interface; overexpression promotes export while siRNA depletion reduces export rates.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, overexpression, fluorescence microscopy, nuclear export assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal gain- and loss-of-function with defined export phenotype plus co-IP, Moderate evidence\",\n      \"pmids\": [\"22250199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The carboxy-terminal domain (CTD) of Nup42/hCG1 binds Gle1/hGle1B at an interface distinct from the Gle1-Dbp5/DDX19B interaction site; a Nup42-CTD/Gle1-CTD/Dbp5 trimeric complex forms in the presence of IP6; deletion of NUP42 abrogates Gle1-Dbp5 interaction; Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5/DDX19B ATPase activity in vitro in a nonadditive manner; disruption of Nup42 or IP6 binding interfaces on Gle1/hGle1B leads to defective mRNA export in yeast and human cells.\",\n      \"method\": \"Structure-function analysis, in vitro ATPase stimulation assays, co-immunoprecipitation, genetic deletion, mRNA export assays in yeast and human cells\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro reconstitution of ATPase activation, trimeric complex formation, genetic deletion, functional mRNA export assays in two organisms; Strong evidence\",\n      \"pmids\": [\"28869701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Nup42 prevents nuclear condensation of heat-induced chaperone mRNAs; loss of Nup42 causes temperature- and transcription-dependent nuclear condensation of chaperone mRNAs that are exported but translationally incompetent, leading to impaired chaperone production and thermosensitivity; co-transcriptional mRNP packaging is a critical determinant of condensation in the absence of Nup42.\",\n      \"method\": \"Genome-wide CRISPRi screen (FRep-Seq), fractionation, translation assays, thermosensitivity assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genome-wide screen plus functional validation with defined phenotype, but preprint single-lab study\",\n      \"pmids\": [\"41727045\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"NUP42/hCG1 is a nucleoporin that anchors the mRNA export factor Gle1/hGle1B at the nuclear pore complex by direct high-affinity binding, enabling Gle1 (together with IP6) to activate the DEAD-box ATPase Dbp5/DDX19B for mRNP remodeling during export; it also acts as an accessory factor in CRM1-dependent protein export, docks HIV-1 Vpr at the nuclear envelope via its N-terminal region, and prevents co-transcriptional nuclear condensation of heat-shock chaperone mRNAs to ensure their translational competence.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper and extract discoveries only from KEEP papers.\n\n**Classification:**\n\n**KEEP (about NUP42/hCG1/Rip1p - the nucleoporin):**\n- PMID:12228227 — hCG1 interaction with HIV-1 Vpr ✓\n- PMID:16000379 — hCG1/hGle1B interaction in mRNA export ✓\n- PMID:28869701 — Nup42 and IP6 coordinate Gle1 stimulation of Dbp5 ✓\n- PMID:22250199 — NLP1/hCG1 promotes CRM1-dependent export ✓\n- PMID:10610322 — Rip1p (yeast ortholog of hCG1/Nup42) interaction with Gle1p ✓\n- PMID:41727045 — Nup42 safeguards heat-induced mRNAs (preprint) ✓\n\n**EXCLUDE (alias collision or off-target):**\n- PMID:10989140 — cg1 in Plasmodium falciparum (CQR gene, no relation)\n- PMID:8075408 — CG-1 from parsley (plant DNA-binding protein, symbol collision)\n- PMID:30171004 — Dehalococcoides mccartyi CG1 (bacterial strain, symbol collision)\n- PMID:23825327 — Enterococcus fecalis CG1.0007 (bacterial strain)\n- PMID:38402932 — Dehalococcoides mccartyi CG1 (bacterial strain)\n- PMID:33020260 — VirE2-CG1 in Agrobacterium/plant context (plant nucleoporin CG1, symbol collision in plants)\n- PMID:12788725 — pCg1 plasmid in Pseudomonas putida (bacterial)\n- PMID:15278309 — nahR in Pseudomonas putida Cg1 (bacterial)\n- PMID:26358603 — Kerstersia gyiorum CG1 (bacterial)\n- PMID:2703383 — NLP-1 drug compound (not a protein)\n- PMID:35271311 — OpenCell (large interactome resource, no NUP42-specific mechanistic finding)\n- PMID:24927568 — BioID NPC (no specific NUP42 mechanistic finding)\n- PMID:26186194 — BioPlex (large interactome, no NUP42-specific mechanism)\n- PMID:28514442 — BioPlex 2.0 (large interactome)\n- PMID:33961781 — BioPlex 3.0 (large interactome)\n- PMID:32296183 — HuRI (large interactome)\n- PMID:26496610 — Human interactome (large interactome)\n- PMID:29395067 — mRNA granules BioID (no NUP42-specific mechanism)\n- PMID:34079125 — Human cell BioID map (no NUP42-specific mechanism)\n- PMID:26912792 — BioID2 method paper\n- PMID:32344865 — BioID/TurboID comparison\n- PMID:19615732 — Dub interactome (no NUP42-specific mechanism)\n- PMID:21145461 — CRL network (no NUP42-specific mechanism)\n- PMID:32807901 — UFMylation/p53 (no NUP42)\n- PMID:20936779 — MAPK interactome (no NUP42 mechanism)\n- PMID:31871319 — Rho GTPase proximity (no NUP42 mechanism)\n- PMID:32203420 — RhoGEF/RhoGAP (no NUP42)\n- PMID:25544563 — KSHV host interactions (no NUP42 mechanism)\n- PMID:18461144 — miRNA/Ago2 (no NUP42)\n- PMID:21873635 — GO annotation (no NUP42-specific mechanism)\n- PMID:10228171 — Mex67p/TAP export (mentions NPC generally, no NUP42-specific mechanism)\n- PMID:12477932 — MGC cDNA sequences (no mechanistic finding)\n- PMID:15489334 — MGC project (no mechanistic finding)\n- PMID:12690205 — Chr7 sequence (no mechanistic finding)\n- PMID:22681889 — mRNA-bound proteome (no NUP42-specific mechanism)\n- PMID:11691994 — Vpr NE disruption (no NUP42-specific mechanism)\n- PMID:9621063 — Vpr/NPC interaction (FG repeats generally, no NUP42-specific mechanism)\n- PMID:10601273 — Glucokinase nuclear import (no NUP42)\n- PMID:24315095 — NPC scaffold structure (no NUP42-specific mechanism)\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"The yeast FG-nucleoporin Rip1p (the S. cerevisiae ortholog of hCG1/NUP42) physically interacts with the C-terminal domain of the mRNA export factor Gle1p and with the DEAD-box protein Rat8p/Dbp5p on the cytoplasmic fibrils of the NPC. High-copy expression of Rip1p suppresses a GLE1 mutant. Rip1p contributes to the association of Gle1p with the pore, which in turn provides a binding site for Rat8p/Dbp5p, placing these factors in a terminal step of mRNA export. A human functional homologue of Rip1p, hCG1, rescues rip1Δ function in yeast, demonstrating evolutionary conservation.\",\n      \"method\": \"Genetic suppressor screen (high-copy suppression of gle1 mutant), co-immunoprecipitation, immunoelectron microscopy localization, yeast complementation assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal genetic and biochemical approaches replicated across multiple methods in same study, with cross-species complementation confirming conservation\",\n      \"pmids\": [\"10610322\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"HIV-1 Vpr docks at the nuclear envelope by interacting with the human nucleoporin hCG1 (NUP42). This interaction was identified by yeast two-hybrid, confirmed in vitro and in transfected cells. The interaction involves the N-terminal region of hCG1, not its FG-repeat domain. Using a nuclear import assay in digitonin-permeabilized cells, hCG1 was shown to participate in docking Vpr at the nuclear envelope.\",\n      \"method\": \"Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation in transfected cells, digitonin-permeabilized cell nuclear import assay, FRAP/photobleaching in live cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Y2H, in vitro, cellular co-IP, functional import assay) in single study with rigorous controls\",\n      \"pmids\": [\"12228227\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The unique C-terminal 43 amino acid region of the hGle1B isoform binds specifically to the C-terminal non-FG region of hCG1 (NUP42). hNup155, hGle1B, and hCG1 form a heterotrimeric complex in vitro. siRNA-mediated depletion of hCG1 causes hGle1 accumulation in cytoplasmic foci and inhibits heat shock-induced Hsp70 mRNA export and Hsp70 protein production in HeLa cells, closely paralleling the role of the yeast ortholog Nup42/Rip1.\",\n      \"method\": \"Co-immunoprecipitation, in vitro complex reconstitution (heterotrimeric complex), siRNA knockdown, mRNA export assay (Hsp70 mRNA FISH), protein level analysis by immunoblot\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vitro complex reconstitution plus siRNA loss-of-function with specific export phenotype, corroborated by yeast ortholog function\",\n      \"pmids\": [\"16000379\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The nucleoporin-like protein NLP1 (hCG1/NUP42) localizes to the nuclear envelope and promotes CRM1-dependent nuclear protein export. NLP1 facilitates formation of trimeric complexes containing CRM1, RanGTP, and NES-containing cargo. These complexes can be dissociated by RanBP1 and/or Nup214. The FG repeats of NLP1 are not required for CRM1 binding. Overexpression of NLP1 enhances CRM1-dependent cargo export, while siRNA depletion reduces export rates.\",\n      \"method\": \"Immunofluorescence localization, co-immunoprecipitation, siRNA knockdown with nuclear export assay, overexpression with export assay, domain deletion mutagenesis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal gain- and loss-of-function experiments with defined export phenotype, domain mutagenesis, and protein complex characterization\",\n      \"pmids\": [\"22250199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Nup42 is required for Gle1-mediated activation of the DEAD-box ATPase Dbp5 (hDDX19B) during mRNA export. The Nup42 carboxy-terminal domain (CTD) binds Gle1/hGle1B at a site distinct from the Gle1-Dbp5/DDX19B interaction interface, and a trimeric Nup42-CTD/Gle1-CTD/Dbp5 complex forms in the presence of IP6. Deletion of NUP42 abrogates the Gle1-Dbp5 interaction. In vitro, Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5 and DDX19B in a nonadditive manner, indicating they act through a shared mechanism. Disruption of Nup42 or IP6 binding interfaces on Gle1/hGle1B impairs mRNA export in both S. cerevisiae and human cells. This mechanism is completely conserved between yeast and humans.\",\n      \"method\": \"In vitro ATPase stimulation assay (reconstitution with recombinant proteins), co-immunoprecipitation, yeast genetic deletion and structure-function analysis, siRNA/overexpression in human cells, mRNA export assay, domain mutagenesis\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution of trimeric complex and ATPase activation, combined with genetic loss-of-function and domain mutagenesis across two species\",\n      \"pmids\": [\"28869701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Nup42 is the strongest suppressor of heat-induced mRNA condensation identified in a whole-genome CRISPRi screen. Loss of Nup42 causes temperature- and transcription-dependent nuclear condensation of chaperone mRNAs (e.g., HSP70); these mRNAs are exported but remain translationally incompetent, leading to impaired chaperone production and thermosensitivity. Co-transcriptional mRNP packaging is a critical determinant of condensation in the absence of Nup42, revealing a nuclear, translation-independent layer of mRNP solubility control that selectively enables heat shock gene expression.\",\n      \"method\": \"Whole-genome CRISPRi screen (FRep-Seq platform), mRNA fractionation, live-cell imaging, translation assay, thermosensitivity phenotyping, transcription inhibition experiments\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — genome-wide screen plus multiple orthogonal functional readouts, but preprint not yet peer-reviewed\",\n      \"pmids\": [\"41727045\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"NUP42 (hCG1/Rip1p) is an FG-nucleoporin located on the cytoplasmic face of the nuclear pore complex that acts as a scaffold to anchor the mRNA export factor Gle1/hGle1B at the NPC, where Gle1 and IP6 together activate the DEAD-box ATPase Dbp5/DDX19B to remodel mRNPs during mRNA export; additionally, NUP42 promotes CRM1-dependent protein export, docks HIV-1 Vpr at the nuclear envelope via the N-terminal region of hCG1, and safeguards heat-induced chaperone mRNAs from nuclear condensation to enable their translation during heat shock.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP42 (hCG1/NLP1) is a nucleoporin that functions as a scaffold for mRNA export and an accessory factor in CRM1-dependent protein export at the nuclear pore complex. Its C-terminal domain directly binds the mRNA export factor Gle1/hGle1B and, together with IP6, stimulates Gle1-mediated activation of the DEAD-box ATPase Dbp5/DDX19B, forming a trimeric Nup42-CTD/Gle1-CTD/Dbp5 complex essential for mRNP remodeling during export; depletion of NUP42 mislocalizes Gle1 to cytoplasmic foci and blocks mRNA export [PMID:16000379, PMID:28869701]. NUP42 also promotes formation of CRM1-RanGTP export complexes through a mechanism independent of its FG repeats, functioning as an accessory factor in CRM1-dependent nuclear protein export [PMID:22250199]. The N-terminal region of NUP42 serves as a docking site for HIV-1 Vpr at the nuclear envelope, mediating Vpr nuclear import [PMID:12228227].\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Whether NUP42 had functions beyond passive transport channel lining was unknown; the demonstration that HIV-1 Vpr binds the N-terminal (non-FG) region of hCG1/NUP42 and uses it as a nuclear envelope docking site for import established NUP42 as an active participant in nuclear transport.\",\n      \"evidence\": \"Yeast two-hybrid, in vitro binding, co-IP, and nuclear import assay in digitonin-permeabilized cells\",\n      \"pmids\": [\"12228227\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Vpr docking at NUP42 represents a hijacked endogenous cargo pathway is unclear\",\n        \"The endogenous ligand or cargo for the NUP42 N-terminal region is not identified\"\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"How Gle1 is anchored at the NPC cytoplasmic face was unresolved; identification of a direct interaction between the hGle1B C-terminal 43 residues and the NUP42 C-terminal non-FG region, and formation of a hNup155/hGle1B/hCG1 heterotrimer, established NUP42 as the essential docking platform for Gle1 at the pore, required for mRNA export.\",\n      \"evidence\": \"In vitro binding assays, co-immunoprecipitation, siRNA knockdown with mRNA export readout (Hsp70 mRNA), fluorescence microscopy\",\n      \"pmids\": [\"16000379\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether NUP42 is required for export of all mRNAs or a subset was not determined\",\n        \"The structural basis of the NUP42–Gle1 interaction was not yet resolved\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Whether NUP42 contributed to protein export in addition to mRNA export was unknown; gain- and loss-of-function experiments showed NUP42 promotes CRM1-RanGTP export complex assembly through a non-FG-repeat interface, establishing it as an accessory factor in CRM1-dependent protein export.\",\n      \"evidence\": \"Co-immunoprecipitation, siRNA knockdown, overexpression, fluorescence microscopy, nuclear export assays\",\n      \"pmids\": [\"22250199\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular interface between NUP42 and CRM1 is undefined\",\n        \"Whether the mRNA export and CRM1 export roles are coordinated or independent is not established\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"How NUP42 mechanistically contributes to Dbp5 ATPase activation during mRNA export was unresolved; reconstitution of a Nup42-CTD/Gle1-CTD/Dbp5 trimeric complex showed that NUP42 and IP6 non-additively stimulate Gle1-dependent Dbp5 ATPase activity, and disruption of these interfaces causes mRNA export defects in both yeast and human cells.\",\n      \"evidence\": \"In vitro ATPase stimulation assays, structure-function analysis, co-IP, genetic deletion in yeast, mRNA export assays in yeast and human cells\",\n      \"pmids\": [\"28869701\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Atomic-resolution structure of the full trimeric complex is not available\",\n        \"How IP6 and NUP42 binding to Gle1 are allosterically coupled is not defined\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Whether NUP42 has post-export functions affecting mRNP quality was unknown; a genome-wide screen revealed that Nup42 loss causes co-transcriptional nuclear condensation of heat-shock chaperone mRNAs that, even if exported, are translationally incompetent, establishing NUP42 as a guardian of mRNP packaging competence.\",\n      \"evidence\": \"Genome-wide CRISPRi screen (FRep-Seq), fractionation, translation assays, thermosensitivity assays (preprint)\",\n      \"pmids\": [\"41727045\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint, not yet peer-reviewed\",\n        \"Whether the condensation-prevention role is direct or mediated through Gle1/Dbp5 is not determined\",\n        \"The scope of mRNAs affected beyond heat-shock chaperones is not defined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A high-resolution structural model of the full NUP42 within the NPC context, the mechanism by which NUP42 prevents mRNP condensation, and the relationship between its distinct mRNA export, CRM1 export, and mRNP quality control roles remain to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No full-length structural model of NUP42 in the NPC context\",\n        \"Mechanism of mRNP condensation prevention is unknown\",\n        \"Whether the CRM1 and Gle1/Dbp5 pathways share a common NUP42 interface is unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005654\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"complexes\": [\n      \"Nuclear Pore Complex (NPC)\",\n      \"Nup42-CTD/Gle1-CTD/Dbp5 trimeric complex\",\n      \"hNup155/hGle1B/hCG1 heterotrimer\"\n    ],\n    \"partners\": [\n      \"GLE1\",\n      \"DDX19B\",\n      \"NUP155\",\n      \"XPO1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"NUP42 (hCG1/Rip1p) is an FG-nucleoporin on the cytoplasmic face of the nuclear pore complex that serves as a scaffold anchoring the mRNA export factor Gle1/hGle1B at the NPC, where the Nup42 C-terminal domain, Gle1, and inositol hexakisphosphate cooperatively stimulate the DEAD-box ATPase Dbp5/DDX19B to remodel mRNPs during the terminal step of mRNA export [PMID:10610322, PMID:28869701]. Nup42 forms a heterotrimeric complex with hNup155 and hGle1B, and its depletion causes cytoplasmic mislocalization of Gle1 and specifically impairs heat-shock-induced Hsp70 mRNA export and chaperone protein production [PMID:16000379]. Independent of its mRNA export role, Nup42 promotes CRM1-dependent nuclear protein export by facilitating trimeric CRM1–RanGTP–NES-cargo complex formation through a mechanism that does not require its FG repeats [PMID:22250199]. The N-terminal region of Nup42 also serves as a docking site for HIV-1 Vpr at the nuclear envelope [PMID:12228227].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Establishing that Nup42/Rip1p physically links Gle1p and Dbp5p at the cytoplasmic face of the NPC answered how these mRNA export factors are recruited to the terminal export step, and cross-species complementation by human hCG1 demonstrated evolutionary conservation.\",\n      \"evidence\": \"Genetic suppressor screen, co-immunoprecipitation, immuno-EM, and yeast complementation in S. cerevisiae and human cells\",\n      \"pmids\": [\"10610322\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Biochemical mechanism by which Nup42 potentiates Dbp5 ATPase activity was not determined\",\n        \"Direct binding interfaces on Nup42 for Gle1 versus Dbp5 were not mapped\",\n        \"Bulk versus transcript-specific mRNA export contribution was unclear\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identification of hCG1/NUP42 as the nuclear envelope docking factor for HIV-1 Vpr revealed an unexpected viral exploitation of this nucleoporin, mapping the interaction to the N-terminal non-FG region.\",\n      \"evidence\": \"Yeast two-hybrid, in vitro binding, co-IP in transfected cells, and digitonin-permeabilized cell import assay\",\n      \"pmids\": [\"12228227\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Vpr docking through Nup42 contributes to viral nuclear import or NPC disruption was not resolved\",\n        \"Structural basis of the Vpr–hCG1 interaction was not determined\"\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstrating that the hGle1B C-terminal tail binds the non-FG region of hCG1 and that their depletion blocks heat-shock Hsp70 mRNA export established that the yeast Nup42–Gle1 export axis is functionally conserved in human cells with transcript-selective consequences.\",\n      \"evidence\": \"In vitro reconstitution of hNup155–hGle1B–hCG1 heterotrimer, siRNA knockdown in HeLa cells, Hsp70 mRNA FISH, and immunoblot\",\n      \"pmids\": [\"16000379\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether Nup42 loss affects bulk poly(A)+ mRNA export or only specific transcripts was not fully resolved\",\n        \"Role of hNup155 within the trimeric complex was not functionally dissected\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Discovery that NUP42/NLP1 promotes CRM1-dependent protein export independently of its FG repeats broadened Nup42 function beyond mRNA export and identified it as a facilitator of CRM1–RanGTP–NES-cargo complex assembly.\",\n      \"evidence\": \"Gain- and loss-of-function experiments (overexpression and siRNA), domain deletion mutagenesis, co-IP with CRM1 complexes, and nuclear export assays\",\n      \"pmids\": [\"22250199\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the mRNA export and CRM1-dependent protein export functions are mechanistically coupled or independent was not tested\",\n        \"Structural basis of CRM1 binding to the non-FG region of Nup42 was not defined\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Biochemical reconstitution of the Nup42-CTD/Gle1/Dbp5 trimeric complex with IP6 resolved the long-standing question of how Nup42 potentiates Gle1-mediated activation of Dbp5/DDX19B ATPase activity, showing Nup42 and IP6 act through a shared, non-additive mechanism conserved from yeast to humans.\",\n      \"evidence\": \"In vitro ATPase stimulation with recombinant proteins, co-IP, domain mutagenesis, yeast genetics, siRNA in human cells, and mRNA export assays across two species\",\n      \"pmids\": [\"28869701\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Atomic-resolution structure of the full Nup42-CTD/Gle1/Dbp5/IP6 complex was not available\",\n        \"Whether Nup42-mediated Dbp5 activation is transcript-selective was not addressed\"\n      ]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"A genome-wide CRISPRi screen identified Nup42 as the top suppressor of heat-induced mRNA condensation, revealing that beyond mRNA export, Nup42 safeguards co-transcriptional mRNP solubility of chaperone transcripts to enable their translation during heat shock. (preprint)\",\n      \"evidence\": \"CRISPRi screen (FRep-Seq), mRNA fractionation, live-cell imaging, translation assays, and transcription inhibition experiments (preprint)\",\n      \"pmids\": [\"41727045\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Findings await peer review\",\n        \"Direct molecular mechanism by which Nup42 prevents mRNA condensation (e.g., through mRNP remodeling or chaperoning) is unknown\",\n        \"Whether this mRNP solubility function operates through the Gle1–Dbp5 axis or an independent pathway was not determined\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"A unifying structural and mechanistic model explaining how Nup42 coordinates its dual roles in mRNA export (Gle1/Dbp5 activation), CRM1-dependent protein export, viral docking, and mRNP solubility control remains to be established.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No high-resolution structure of full-length Nup42 in complex with its partners exists\",\n        \"Whether the mRNA export, CRM1 export, and mRNP solubility functions compete for the same Nup42 pools or operate through distinct sub-complexes is unknown\",\n        \"In vivo contribution of Nup42 to bulk versus heat-shock-specific mRNA export in mammalian tissues has not been assessed\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 2, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 4]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3, 4]}\n    ],\n    \"complexes\": [\n      \"Nuclear pore complex (NPC)\",\n      \"Nup42/Gle1/Dbp5 trimeric complex\",\n      \"hNup155/hGle1B/hCG1 heterotrimer\"\n    ],\n    \"partners\": [\n      \"GLE1\",\n      \"DBP5\",\n      \"DDX19B\",\n      \"NUP155\",\n      \"XPO1\",\n      \"NUP214\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}