Affinage

PTBP1

Polypyrimidine tract-binding protein 1 · UniProt P26599

Length
557 aa
Mass
59.6 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 51 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTBP1 (hnRNP I) is a polypyrimidine/CU-rich-tract-binding RNA protein that governs alternative splicing and a broader post-transcriptional program controlling cell proliferation, differentiation, and tissue development (PMID:1641332, PMID:27681424, PMID:36958328). As a splicing regulator it represses cryptic and tissue-specific cassette exons through CU microsatellite elements (PMID:27681424), with the splicing outcome dictated by positional rules: PTBP1-associated RNA loops within a single intron accelerate asymmetric intron removal to promote exon inclusion, whereas loops spanning a cassette exon repress it (PMID:36958328). It can also antagonize repression by competing with other splicing factors for intronic elements (PMID:17548433), and acts as an RNA chaperone that compacts and orders structured RNAs such as viral IRES elements (PMID:37833274). Beyond splicing, PTBP1 controls mRNA fate in the cytoplasm: it binds 5'-UTRs to modulate stability or translation of targets including AXL, CCND3, and NCOA4 (PMID:31729427, PMID:31301177, PMID:36660932), destabilizes transcripts such as MCL1 (PMID:27367564), and protects mRNAs from nonsense-mediated decay by promoting ATPase-dependent displacement of UPF1 (PMID:32571872). PTBP1 directs cell-type-specific programs across many tissues — germinal center B-cell proliferation and antibody production (PMID:29358707, PMID:30476084), endothelial NF-κB priming and atherosclerosis through Ripk1 splicing (PMID:35858420), hematopoietic stem cell self-renewal via ribosomal protein translation (PMID:35545054), spermatogonial proliferation (PMID:30416150), and cardiac development, where misregulated NDUFS2 exon skipping impairs mitochondrial complex I and causes dilated cardiomyopathy (PMID:38841852). A recurrent oncogenic theme is PTBP1-driven PKM splicing toward the PKM2 isoform to promote glycolysis (PMID:26980745, PMID:39189621). PTBP1 protein abundance and RNA-binding activity are themselves tuned by post-translational modifications including K266 crotonylation and K436 lactylation, and by ubiquitin-system enzymes such as the deubiquitinase PSMD14 and the E3 ligase TRIM21 (PMID:39497094, PMID:35405117, PMID:39570804).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 Medium

    Established PTBP1 as a nuclear hnRNP that binds polypyrimidine tracts on nascent transcripts, defining its founding biochemical activity.

    Evidence Micrococcal nuclease fractionation of hnRNP complexes and immunofluorescence

    PMID:1641332

    Open questions at the time
    • No splicing or downstream functional readout in this study
    • Perinucleolar localization left mechanistically unexplained
  2. 1997 Medium

    Mapped an N-terminal bipartite nuclear localization domain, explaining how PTBP1 reaches its site of action.

    Evidence Domain-fusion to a cytoplasmic reporter and subcellular localization assay

    PMID:9281380

    Open questions at the time
    • Does not address regulated nuclear/cytoplasmic shuttling
    • No link to function of cytoplasmic pools
  3. 1999 Medium

    Linked PTBP1 to cytoplasmic mRNA localization, showing it binds a localization element required for vegetal RNA transport.

    Evidence Reciprocal in vitro RNA binding and in vivo colocalization in Xenopus oocytes

    PMID:10518224 PMID:18039852

    Open questions at the time
    • Mechanism of RNP remodeling not resolved at this stage
    • Generality to mammalian mRNA localization untested
  4. 2007 High

    Demonstrated PTBP1 acts as a positional splicing regulator that can both repress and, by competing with other factors, activate splice-site usage.

    Evidence RNA affinity chromatography with in vitro and in vivo splicing reporters

    PMID:17548433

    Open questions at the time
    • Single element studied; positional logic not yet generalized
    • Cofactor competition not structurally defined
  5. 2009 Medium

    Connected PTBP1 to disease-relevant phenotypes by showing it controls oncogenic exon choices (RTN4) and can destabilize signaling effectors (NICD).

    Evidence Exon array after siRNA knockdown, isoform rescue, and zebrafish genetics

    PMID:19197356 PMID:19506066

    Open questions at the time
    • NICD destabilization mechanism distinct from RNA binding not fully defined
    • Direct binding sites not mapped for all targets
  6. 2016 High

    Defined transcriptome-wide repression of cryptic and tissue-specific exons via CU microsatellites and distinguished PTBP1 from PTBP2 by cofactor usage rather than RNA-binding specificity.

    Evidence RNA-seq after PTBP1/PTBP2 knockdown, motif analysis, and knockin/knockout mouse genetics

    PMID:27681424 PMID:27926877

    Open questions at the time
    • Identity of the distinguishing cofactors not established here
    • Quantitative rules linking binding to outcome not yet derived
  7. 2016 Medium

    Extended PTBP1 function into cytoplasmic mRNA stability control, showing direct binding destabilizes targets such as MCL1 with consequences for apoptosis.

    Evidence RIP, mRNA stability assays, and MCL1 rescue with apoptosis readouts

    PMID:26980745 PMID:27367564

    Open questions at the time
    • Decay machinery recruited by PTBP1 not identified
    • Relationship between stability and splicing roles unresolved
  8. 2018 High

    Established PTBP1 as a developmental and immune regulator, required for germinal center B-cell cell-cycle progression and spermatogonial proliferation.

    Evidence Conditional knockout mice with cell-cycle, immunization, and histology analyses

    PMID:29358707 PMID:30416150 PMID:30476084

    Open questions at the time
    • Direct splicing targets driving each tissue phenotype only partially defined
    • Tissue-specific cofactor context not resolved
  9. 2018 Medium

    Showed PTBP1 activity and levels are regulated by post-translational modifications and by interactions with miRNA/lncRNA machinery.

    Evidence Mass spectrometry of PTMs in splicing reactions; AGO2 Co-IP and miRNA cooperation assays

    PMID:22427970 PMID:29748555 PMID:29851470

    Open questions at the time
    • Functional consequence of individual PTM sites not validated at this stage
    • Writer/eraser enzymes not yet assigned
  10. 2020 High

    Resolved a mechanism by which PTBP1 protects mRNAs from NMD, displacing UPF1 in an ATPase-dependent manner without direct site competition.

    Evidence In vitro helicase/dissociation assays with purified components and transcriptome-wide UPF1 CLIP-seq

    PMID:32571872

    Open questions at the time
    • Which endogenous transcripts are physiologically protected not enumerated
    • Coordination with co-transcriptional splicing not addressed here
  11. 2022 High

    Demonstrated PTBP1 drives vascular and hematopoietic programs through specific splicing events (Ripk1, ribosomal protein translation) with in vivo disease consequences.

    Evidence CRISPR screen, endothelial- and hematopoietic-specific conditional knockouts, splicing and ribosome assays, atherosclerosis model

    PMID:35545054 PMID:35858420

    Open questions at the time
    • Full set of effector splice events per phenotype incomplete
    • Crosstalk between translation and splicing roles unresolved
  12. 2023 High

    Derived the structural and positional logic of PTBP1 splicing regulation via RNA loops, and showed it activates co-transcriptional splicing with epigenetic downstream effects through DNMT3B.

    Evidence CRIC-seq RNA-RNA proximity ligation; acute dTAG depletion with nascent transcript and bisulfite sequencing; integrative structural modeling of an IRES complex

    PMID:36626906 PMID:36958328 PMID:37833274

    Open questions at the time
    • Determinants of loop formation in vivo not fully defined
    • Generality of the chaperone model beyond viral IRES untested
  13. 2024 High

    Showed PTBP1 protein stability and RNA-binding are tuned by metabolic-linked PTMs and ubiquitin-system enzymes, and that PTBP1 controls cardiac and metabolic phenotypes through specific isoform switches.

    Evidence Crotonylation/lactylation proteomics with K266/K436 mutagenesis; PSMD14/TRIM21 Co-IP and ubiquitination assays; conditional knockouts for NDUFS2 and Arrb1 splicing

    PMID:35405117 PMID:37002228 PMID:38841852 PMID:39497094 PMID:39570804

    Open questions at the time
    • Hierarchy among competing PTMs not established
    • How metabolic state feeds back to PTBP1 modification in vivo unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The integrated rules connecting PTBP1 binding position, RNA structure, cofactor identity, and post-translational modification state to a defined splicing or stability outcome in a given cell type remain to be unified into a predictive model.
  • No single framework links positional loop logic, PTM state, and tissue cofactors
  • Causal mechanism distinguishing PTBP1 from PTBP2 outcomes not molecularly resolved
  • Mendelian disease association in humans not established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 7 GO:0045182 translation regulator activity 4 GO:0140098 catalytic activity, acting on RNA 4 GO:0044183 protein folding chaperone 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005654 nucleoplasm 3 GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 1
Partners
AGO2HNRNPA1HNRNPH1MYCPSMD14RALYTRIM21UPF1

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 PTBP1 (hnRNP I) is a nuclear RNA-binding protein that associates with polypyrimidine tracts on hnRNA; it is released from hnRNP complexes by micrococcal nuclease digestion more readily than most hnRNP proteins (nuclease hypersensitivity), suggesting binding to exposed regions of hnRNA-protein complexes. Immunofluorescence revealed a unique localization in the nucleoplasm plus a discrete perinucleolar structure. Micrococcal nuclease digestion of hnRNP complexes; immunofluorescence microscopy; cDNA cloning and sequencing Nucleic acids research Medium 1641332
1997 Nuclear localization of PTBP1 (hnRNP I) is directed by a 60-amino-acid bipartite sequence at the amino terminus (designated NLD-I), which is both necessary and sufficient for nuclear import, as demonstrated by fusion to a cytoplasmic reporter protein. Transient transfection of hnRNP I domain fusions to chloramphenicol acetyltransferase reporter; subcellular localization assay Experimental cell research Medium 9281380
1999 Xenopus PTBP1 homolog VgRBP60 binds the Vg1 mRNA localization element and is required for cytoplasmic RNA localization in Xenopus oocytes; specific base changes that abolish localization in vivo also abolish VgRBP60 binding in vitro, and hnRNP I colocalizes with Vg1 RNA in the vegetal cytoplasm. In vitro RNA-binding assays with mutant localization elements; immunolocalization and in situ hybridization in Xenopus oocytes Molecular cell Medium 10518224
2000 The human HNRNPI gene (chromosome 19) generates three protein isoforms (hnRNP I / PTB, PTB2, PTB3) through alternative splicing of a single gene transcript; the chromosome 14 locus is a non-expressed processed pseudogene. RT-PCR, EST database analysis, genomic DNA sequencing of intron-exon boundaries Gene Medium 11024286
2007 PTB/hnRNP I is required for remodeling of the Vg1 RNP during cytoplasmic RNA transport in Xenopus oocytes; it promotes dissociation of Vg1RBP/vera from Vg1 RNA, and mutations blocking this remodeling event abolish vegetal localization. RNA-protein interaction assays; loss-of-function experiments with remodeling-blocking mutations; vegetal localization assays in Xenopus oocytes Molecular and cellular biology Medium 18039852
2007 PTBP1 (hnRNP I/PTB) can antagonize splicing repression imposed by SRp30c: PTB competes with SRp30c for binding to the CE9 intronic element, reduces SRp30c binding in nuclear extract, stimulates splicing to a downstream 3' splice site, and relieves CE9-mediated splicing repression in vitro and in vivo. RNA affinity chromatography; in vitro splicing assays with His-tagged PTB; in vivo splicing reporter assays RNA High 17548433
2009 Zebrafish hnRNP I (PTBP1 ortholog) inhibits Notch signaling by destabilizing the Notch intracellular domain (NICD); overexpression of hnRNP I promotes NICD turnover requiring the C-terminal RAM domain of NICD, and this activity is conserved from zebrafish to human. Zebrafish brom bones mutant characterization; co-immunoprecipitation; NICD stability/turnover assays; conservation assay in human cells PLoS genetics Medium 19197356
2009 PTBP1 knockdown in human glioma cells slows proliferation and inhibits migration and adhesion; PTBP1 promotes exon 3 skipping of RTN4 (Nogo), and overexpression of the exon-3-containing RTN4 isoform decreases proliferation to a similar degree as PTBP1 removal, placing RTN4 splicing downstream of PTBP1 in glioma growth. siRNA knockdown; Affymetrix Exon Array; isoform overexpression; cell proliferation, migration, and adhesion assays Brain Medium 19506066
2012 PTBP1 interacts with miRNAs (including let-7) and with human Argonaute 2 (hAgo2) through RNA, and genetically interacts with C. elegans let-7 pathway, indicating a conserved role for PTBP1 in modulating miRNA-mediated gene regulation. Biotinylated miRNA inhibitor affinity purification; co-immunoprecipitation; C. elegans genetic interaction assay PloS one Medium 22427970
2015 Linc-RoR interacts with PTBP1 (hnRNP I) and requires PTBP1 to bind c-Myc mRNA, thereby stabilizing c-Myc mRNA and promoting c-Myc expression; this interaction is distinct from Linc-RoR's inhibitory interaction with AUF1. RNA immunoprecipitation; RNA pulldown; c-Myc mRNA stability assays; knockdown/rescue experiments Nucleic acids research Medium 26656491
2016 PTBP1 promotes production of PKM2 (cancer-specific pyruvate kinase isoform) over PKM1 through alternative splicing of the PKM gene; miR-1 and miR-133b suppress this Warburg-effect-promoting activity by silencing PTBP1, switching isoform expression from PKM2 to PKM1 and increasing ROS. Ectopic miRNA expression; isoform-specific RT-PCR for PKM1/PKM2; in vitro and in vivo tumor models; ROS measurement Oncotarget Medium 26980745
2016 PTBP1 and PTBP2 repress non-conserved cryptic exons using CU microsatellites; they also repress conserved tissue-specific exons, with repression titrated to generate transcriptome diversity needed for neuronal differentiation. RNA-seq after PTBP1/PTBP2 knockdown; bioinformatic identification of CU microsatellite binding motifs; minigene splicing assays Cell reports Medium 27681424
2016 PTBP1 and PTBP2 display both redundant and distinct roles in neuronal pre-mRNA splicing; a PTBP1 knockin allele rescues forebrain-specific but not pan-neuronal Ptbp2 knockout, indicating functional differences not arising from differential RNA binding but potentially from different cofactor interactions. Conditional knockin mouse genetics; Ptbp2 knockout; transcriptome-wide RNA binding comparison; behavioral and developmental phenotype analysis Cell reports High 27926877
2016 PTBP1 directly binds MCL1 mRNA and destabilizes it; knockdown of PTBP1 stabilizes MCL1 mRNA, increases MCL1 protein, and protects cancer cells from antitubulin agent-induced apoptosis in a MCL1-dependent manner. RNA immunoprecipitation; mRNA stability assays; PTBP1 knockdown; MCL1 rescue experiments; apoptosis assays Cell death and differentiation Medium 27367564
2016 PTBP1 directly binds the proximal poly(A) signal of CD5 mRNA and affects its stability or poly(A) site selection during T-cell activation, fine-tuning CD5 expression levels. siRNA depletion of PTBP1; quantification of CD5 mRNA isoforms; 3'-UTR reporter assays European journal of immunology Low 27005442
2018 PTBP1 is required for progression of germinal center B cells through late S phase and for affinity maturation; it directly regulates alternative splicing and abundance of transcripts induced during positive selection to promote proliferation. Conditional PTBP1 knockout in B cells; flow cytometry cell cycle analysis; RNA-seq; immunization experiments Nature immunology High 29358707
2018 PTBP1 enhances miR-101-guided AGO2 interaction with MCL1 mRNA, thereby facilitating miR-101-induced MCL1 repression and apoptosis; PTBP1 cooperates with miRISC on a shared target mRNA. Co-immunoprecipitation of AGO2; miR-101 overexpression; PTBP1 knockdown; apoptosis and clonogenic assays Cell death & disease Medium 29748555
2018 PTBP1 and PTBP2 have distinct phosphorylation patterns in their N-terminal, linker 1, and linker 2 regions, and overlapping acetylation in their RRMs with unique sites in PTBP1 RRM2 and RRM3; lysine residues in the PTBP2 nuclear localization sequence are acetylated, suggesting post-translational modifications contribute to their differential splicing activities. Mass spectrometry analysis of PTMs in in vitro splicing reaction mixtures Biochemistry Medium 29851470
2018 PTBP1 promotes full-length hTERT splicing and telomerase activity; knockdown of PTBP1 reduces hTERT FL splicing, shortens telomere length, and PTBP1 interacts with hTERT pre-mRNA in a NOVA1-dependent manner as shown by RNA pulldown. PTBP1 stable knockdown; RT-PCR for hTERT isoforms; RNA pulldown; telomere length measurement Oncogene Medium 30568224
2018 PTBP1 contributes to spermatogenesis by regulating spermatogonia proliferation; germ cell-specific Ptbp1 knockout mice show retarded neonatal spermatogonia proliferation and progressive decline in sperm count, and PTBP1 deletion in germline stem cells causes proliferation arrest and increased apoptosis in vitro. Cre-loxP conditional knockout mice; histology; in vitro germline stem cell culture with hydroxytamoxifen-induced deletion; flow cytometry apoptosis assay The Journal of reproduction and development Medium 30416150
2019 PTBP1 directly binds the 5'-UTR of AXL mRNA via its RRM1 domain and reduces AXL mRNA stability without affecting transcription rate, leading to decreased AXL expression and promoting apoptosis. RNA immunoprecipitation; mRNA stability assays; RRM1 domain mutation; transcription run-on assay; PTBP1/PTBP2 overexpression comparison Scientific reports Medium 31729427
2019 PTBP1 binds to and regulates the stability of SLC31A1 (copper transporter) mRNA, confirmed by RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability detection; knockdown of PTBP1 upregulates SLC31A1 and enhances cisplatin sensitivity in osteosarcoma cells. RNA immunoprecipitation; dual-luciferase reporter assay; mRNA stability assay; transcriptome sequencing; xenograft model Journal of cellular and molecular medicine Medium 32207235
2019 PTBP1 enhances cyclin D3 (CCND3) translation by interacting with the 5'-UTR of CCND3 mRNA, facilitating cell cycle progression in hepatocellular carcinoma cells. RNA immunoprecipitation; luciferase 5'-UTR reporter; PTBP1 knockdown with CCND3 protein measurement The Journal of pathology Medium 31301177
2019 Ptbp1 is essential for BCR-mediated B-cell activation and antibody production; B-cell-specific Ptbp1-deficient mice have severely reduced natural antibodies, defective BCR-mediated activation, and impaired plasmablast generation in response to both T-independent and T-dependent antigens. B-cell-specific conditional knockout mice; serum antibody measurement by ELISA; immunization with NP-Ficoll and NP-CGG; flow cytometry International immunology Medium 30476084
2019 PTBP1 mRNA isoforms differ in their 5'- and 3'-UTRs and protein-coding region splicing; eIF3 binds differentially to each PTBP1 mRNA isoform in a cell-cycle-dependent manner, with eIF3 binding correlating with repression of PTBP1 protein during S phase, indicating translational regulation of PTBP1 levels during the cell cycle. 5'/3' end mapping; ribosome profiling; eIF3 RIP; cell cycle synchronization; Western blot RNA Medium 31263002
2020 PTBP1 promotes ATPase-dependent dissociation of UPF1 from potential NMD target mRNAs, protecting them from nonsense-mediated decay; this mechanism depends on UPF1's tendency to release RNA upon ATP binding/hydrolysis and is coordinated by a regulatory loop in UPF1 domain 1B. PTBP1 does not require direct competition for binding sites but displaces already-bound UPF1. In vitro helicase activity assays; UPF1 dissociation from purified mRNPs; transcriptome-wide UPF1 CLIP-seq; domain mutagenesis of UPF1 The Journal of biological chemistry High 32571872
2020 PTBP1 and HNRNPK are essential RNA-binding proteins for SINEUP lncRNA-mediated translational upregulation; they contribute to SINEUP RNA subcellular distribution and assembly of translational initiation complexes, leading to enhanced target mRNA translation. Co-transfection; subcellular fractionation; co-immunoprecipitation; translation assays in HEK293T cells Nucleic acids research Medium 33130894
2020 LUCAT1 lncRNA interacts with PTBP1 in colorectal cancer cells and facilitates association of DNA damage-related gene transcripts with PTBP1, leading to altered alternative splicing of those genes; ectopic PTBP1 expression rescues the effects of LUCAT1 knockdown. RNA immunoprecipitation; alternative splicing analysis by RNA-seq; PTBP1 rescue experiment; in vivo xenograft Molecular cancer Medium 31964396
2021 PTBP1 is required for germinal center B cells receiving T cell help to express the c-MYC-dependent gene program and to progress through late S phase; it directly regulates alternative splicing and transcript abundance of genes upregulated during positive selection. Conditional PTBP1 knockout; flow cytometry cell cycle analysis; RNA-seq for splicing and transcript abundance; in vivo immunization Nature immunology High 29358707
2021 SON regulates PTBP1-mediated oncogenic splicing in glioblastoma: SON knockdown causes intron retention in the PTBP1 transcript, reducing PTBP1 protein and inhibiting downstream oncogenic splicing events. SON also forms a complex with hnRNP A2B1 and antagonizes RBFOX2 activity. PTBP1 RNA-seq splicing analysis; SON knockdown; RT-PCR for PTBP1 intron retention; co-immunoprecipitation; orthotopic xenograft model Nature communications Medium 34548489
2021 MALAT1 lncRNA interacts with PTBP1 and promotes USP8 mRNA degradation through this interaction; reduced USP8 then regulates ubiquitination and stability of TAK1, promoting macrophage pyroptosis and inflammation in liver fibrosis. RNA pulldown; RNA immunoprecipitation; mRNA stability assay; co-immunoprecipitation; protein degradation assay; m6A methylated RIP Cell death discovery Medium 34839365
2021 PTBP1 deficiency in dendritic cells increases MHC II expression, perturbs T-cell homeostasis, and regulates PKM alternative splicing and a subset of IFN response genes without affecting DC development. DC-specific Ptbp1 conditional knockout; flow cytometry; RNA-seq for splicing; antitumor and asthma models Immunology Medium 33421118
2022 Ptbp1 deficiency in endothelial cells reverses low-disturbed-flow-induced RNA splicing patterns in the NF-κB pathway and inhibits NF-κB nuclear translocation and transcriptional activation of Icam1 and Vcam1; endothelial-specific Ptbp1 deletion reduces myeloid cell infiltration and atherosclerosis in vivo; Ptbp1 promotes inclusion of a conserved alternative exon in Ripk1, reducing Ripk1 protein. CRISPR Cas9 KO screen; endothelial-specific conditional knockout; RNA splicing analysis; NF-κB nuclear translocation assay; in vivo atherosclerosis model Proceedings of the National Academy of Sciences High 35858420
2022 PTBP1 promotes hematopoietic stem cell self-renewal and erythroid differentiation by ensuring ribosome biogenesis and translation of mRNAs encoding ribosomal proteins; PTBP1 deficiency causes splicing defects and upregulation of a specific CDC42 isoform that partly mimics the protein-synthesis defect. Hematopoietic compartment-specific PTBP1 deletion; RNA-seq for splicing; ribosome biogenesis assays; polysome profiling; CDC42 isoform overexpression Cell reports Medium 35545054
2022 PTBP1 interacts with hnRNPH1 in Sertoli cells to regulate alternative pre-mRNA splicing of cell adhesion-related target genes; this interaction is required for blood-testis barrier function and normal spermatogenesis. Sertoli cell-specific hnRNPH1 knockout; co-immunoprecipitation; alternative splicing analysis by RNA-seq Development Medium 36718792
2022 PTBP1 and PTBP2 interact with distinct sets of proteins under splicing conditions: PTBP1 interacts with many mRNA processing and splicing regulators while PTBP2 does not; both interact with chromatin remodeling and transcription proteins; potential 'writers' and 'erasers' of PTM modifications on PTBPs were identified. In vitro splicing system; mass spectrometry identification of interacting proteins PloS one Medium 35113929
2023 Integrative structural modeling of PTBP1 bound to an EMCV IRES RNA fragment reveals strong compaction and ordering of both RNA and protein with residual conformational flexibility; PTBP1 acts as an RNA chaperone organizing the IRES RNA into a few distinct conformations with RNA stems exposed outward. NMR; mass spectrometry; small-angle scattering; integrative structural modeling Nature communications High 37833274
2023 PTBP1-associated RNA loops determined by CRIC-seq reveal positional rules: loops within individual introns promote cassette exon inclusion by accelerating asymmetric intron removal, while loops spanning across cassette exons repress splicing; cancer-related splicing QTLs can disrupt these RNA loops by reducing PTBP1 binding. Capture RIC-seq (CRIC-seq) for in situ RNA-RNA proximity ligation; bioinformatic analysis of loop positions; splicing outcome prediction Molecular cell High 36958328
2023 PTBP1 activates co-transcriptional splicing of hundreds of introns in pluripotent stem cells; retention of a PTBP1-dependent intron in DNMT3B triggers NMD of DNMT3B transcripts, reducing DNMT3B levels in developing neurons and protecting differentiation-specific genes from ectopic methylation. Acute PTBP1 depletion (dTAG system); analysis of chromatin- and RNA Pol II-associated nascent transcripts; RNA-seq; bisulfite sequencing for methylation Molecular cell High 36626906
2023 In adult peripheral sensory neurons, PTBP1 is co-expressed with PTBP2 (PTBP2 restricted to nucleus, PTBP1 also axonal); axonal PTBP1 levels increase after peripheral nerve injury, where it associates with mRNAs for importin β1 (KPNB1) and RHOA; PTBP1 perturbation affects local axonal translation, nociceptor regeneration, and thermal/mechanical sensation. Immunofluorescence and subcellular fractionation; axonal mRNA co-IP; local translation assays; sensory phenotyping after PTBP1 perturbation Science advances Medium 37506203
2023 PTBP1 directly binds the 5'-UTR of NCOA4 mRNA and promotes NCOA4 translation, thereby mediating ferroptosis in liver cancer cells; the PTBP1-binding region was mapped to the 5'-UTR by RNA pulldown, and PTBP1 silencing decreases NCOA4-mediated ferritinophagy. RNA pulldown; dual-luciferase assay; cycloheximide chase (PTBP1 KD did not affect NCOA4 protein stability); xenograft model Oncology reports Medium 36660932
2023 PTBP1 interacts with RALY to regulate exon 5 splicing of DNMT3B (from DNMT3B-S to DNMT3B-L isoform); DNMT3B-L then induces promoter methylation of DUSP2, suppressing DUSP2 expression and increasing radioresistance in prostate cancer cells. Co-immunoprecipitation; splicing analysis by RT-PCR; PTBP1/RALY knockdown; bisulfite sequencing; in vitro and in vivo irradiation models Advanced science Medium 39287090
2023 MIR99AHG lncRNA binds and stabilizes PTBP1, and the complex promotes inclusion of exon 13 in SMARCA1 pre-mRNA (producing SMARCA1-L isoform) by altering PTBP1 binding to splice sites on intron 12; SMARCA1-L, unlike SMARCA1, promotes invadopodia formation and invasion in colorectal cancer. RNA pulldown; RNA immunoprecipitation; splicing minigene assays; MIR99AHG knockdown; invasion assays; patient CRC tissue analysis Science signaling Medium 37725664
2024 PTBP1 inhibits NDUFS2 third exon skipping in cardiomyocytes by directly binding to PTBP1 in the nucleus; loss of DCRT lncRNA releases PTBP1 to promote NDUFS2 exon skipping, and the resulting NDUFS2 isoform impairs mitochondrial complex I activity and antioxidant function, causing dilated cardiomyopathy. CRISPR-Cas9 DCRT knockout mice; RNA immunoprecipitation; chromatin co-IP; isoform sequencing; mitochondrial complex I activity assay Circulation High 38841852
2024 PTBP1 K266 crotonylation (by KAT2B) enhances PTBP1 interaction with hnRNPA1/A2 and promotes PKM alternative splicing toward PKM2, increasing glycolysis and colorectal cancer progression; K266 crotonylation also enhances RNA-binding capacity. Crotonylation proteomics; immunoprecipitation; RNA immunoprecipitation; point mutagenesis (K266); in vitro/in vivo CRC models Journal of translational medicine Medium 39497094
2024 PTBP1 deficiency in endothelial cells leads to left ventricular noncompaction by reducing endothelial cell migration via altered alternative splicing of β-arrestin-1 (Arrb1), which disrupts cardiomyocyte proliferation during cardiac development. Endothelial-specific Ptbp1 conditional knockout; RNA splicing analysis; migration assays; cardiac morphology/histology Nature communications Medium 37002228
2024 PSMD14 (a deubiquitinating enzyme) directly interacts with PTBP1, promotes its deubiquitination and stabilization, and thereby sustains PTBP1 protein levels to promote gastric cancer progression. Co-immunoprecipitation; ubiquitination assay; Western blot; PSMD14/PTBP1 knockdown and rescue Experimental cell research Medium 35405117
2025 PTBP1 K436 lactylation (with SIRT1 as eraser) stabilizes PTBP1 protein by attenuating interaction with TRIM21 E3 ligase and inhibiting proteasomal degradation; K436 lactylation also enhances PTBP1 RNA-binding capacity and promotes PFKFB4 mRNA stabilization, further increasing glycolysis in glioma stem cells. Lactylation proteomics; site-directed mutagenesis (K436); Co-IP of PTBP1/TRIM21; RNA immunoprecipitation for PFKFB4; SIRT1 delactylation assay; GSC functional assays Cancer research Medium 39570804
2024 PTBP1 stabilizes TXNIP mRNA by direct binding; PTBP1 knockdown promotes TXNIP mRNA stability, increasing TXNIP-mediated oxidative stress that impairs lysosomal function and blocks autophagic flux in gastric cancer cells. RNA immunoprecipitation sequencing (si-PTBP1 RIP-seq); mRNA stability assay; ROS and autophagy flux assays; xenograft Cellular & molecular biology letters Medium 39153986
2024 Lkb1 regulates PTBP1 expression and through PTBP1 controls alternative splicing of PKM isoforms 1 and 2 in vascular smooth muscle cells; loss of Lkb1 increases PKM2/PKM1 ratio and aerobic glycolysis, driving VSMC transdifferentiation and aortic aneurysm; treatment with PKM2 activator rescues the phenotype. Smooth muscle cell-specific Lkb1 conditional knockout; single-cell RNA-seq; isoform-specific RT-PCR; PKM2 activator rescue; lineage tracing Cardiovascular research Medium 39189621
2017 PTBP1 directly interacts with c-Myc protein and stabilizes c-Myc by preventing its proteasomal degradation; this is mediated by PTBP1 upregulating USP28 and limiting FBW7-mediated ubiquitination of c-Myc in gastric cancer cells. Co-immunoprecipitation; ubiquitination assay; Western blot; PTBP1/c-Myc knockdown and rescue British journal of cancer Medium 36635500

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs. Nucleic acids research 302 1641332
1999 A Xenopus protein related to hnRNP I has a role in cytoplasmic RNA localization. Molecular cell 202 10518224
2020 Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response. Molecular cancer 136 31964396
2021 The METTL3/MALAT1/PTBP1/USP8/TAK1 axis promotes pyroptosis and M1 polarization of macrophages and contributes to liver fibrosis. Cell death discovery 128 34839365
2009 Splicing factors PTBP1 and PTBP2 promote proliferation and migration of glioma cell lines. Brain : a journal of neurology 127 19506066
2020 Roles of PTBP1 in alternative splicing, glycolysis, and oncogensis. Journal of Zhejiang University. Science. B 120 32115910
2016 PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing. Cell reports 105 27926877
2015 Linc-RoR promotes c-Myc expression through hnRNP I and AUF1. Nucleic acids research 98 26656491
2018 PTBP1 promotes the growth of breast cancer cells through the PTEN/Akt pathway and autophagy. Journal of cellular physiology 78 29856478
2018 The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers. Nature immunology 74 29358707
2016 PTBP1-associated microRNA-1 and -133b suppress the Warburg effect in colorectal tumors. Oncotarget 70 26980745
2008 Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2. EMBO reports 70 18833287
2016 PTBP1 and PTBP2 Repress Nonconserved Cryptic Exons. Cell reports 62 27681424
2023 CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export. Cell death & disease 59 36635270
2025 PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis. Cancer research 58 39570804
2019 LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1. Oncogenesis 57 31822653
2020 PTBP1 modulates osteosarcoma chemoresistance to cisplatin by regulating the expression of the copper transporter SLC31A1. Journal of cellular and molecular medicine 55 32207235
2022 Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina. Cell reports 54 35705053
2019 MiR-326 Inhibits Inflammation and Promotes Autophagy in Silica-Induced Pulmonary Fibrosis through Targeting TNFSF14 and PTBP1. Chemical research in toxicology 52 31642316
2023 An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma. Nature cancer 51 37845485
2023 LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement. Journal of experimental & clinical cancer research : CR 48 37740243
2020 SINEUP long non-coding RNA acts via PTBP1 and HNRNPK to promote translational initiation assemblies. Nucleic acids research 48 33130894
2020 PTBP1-targeting microRNAs regulate cancer-specific energy metabolism through the modulation of PKM1/M2 splicing. Cancer science 47 33070451
2020 The RNA-binding protein PTBP1 promotes ATPase-dependent dissociation of the RNA helicase UPF1 to protect transcripts from nonsense-mediated mRNA decay. The Journal of biological chemistry 45 32571872
2018 NOVA1 directs PTBP1 to hTERT pre-mRNA and promotes telomerase activity in cancer cells. Oncogene 44 30568224
2016 PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics. Cell death and differentiation 44 27367564
2007 PTB/hnRNP I is required for RNP remodeling during RNA localization in Xenopus oocytes. Molecular and cellular biology 43 18039852
2019 Biosynthetic CircRNA_001160 induced by PTBP1 regulates the permeability of BTB via the CircRNA_001160/miR-195-5p/ETV1 axis. Cell death & disease 41 31862871
2007 hnRNP I/PTB can antagonize the splicing repressor activity of SRp30c. RNA (New York, N.Y.) 41 17548433
2019 A miR-194/PTBP1/CCND3 axis regulates tumor growth in human hepatocellular carcinoma. The Journal of pathology 40 31301177
2022 Reduced CircSMOC1 Level Promotes Metabolic Reprogramming via PTBP1 (Polypyrimidine Tract-Binding Protein) and miR-329-3p in Pulmonary Arterial Hypertension Rats. Hypertension (Dallas, Tex. : 1979) 39 35997022
2021 SON drives oncogenic RNA splicing in glioblastoma by regulating PTBP1/PTBP2 switching and RBFOX2 activity. Nature communications 38 34548489
2019 PTBP1-mediated regulation of AXL mRNA stability plays a role in lung tumorigenesis. Scientific reports 38 31729427
2022 Critical examination of Ptbp1-mediated glia-to-neuron conversion in the mouse retina. Cell reports 37 35705044
2019 PTBP1 mRNA isoforms and regulation of their translation. RNA (New York, N.Y.) 37 31263002
2016 CD5 expression is regulated during human T-cell activation by alternative polyadenylation, PTBP1, and miR-204. European journal of immunology 37 27005442
2022 METTL3-modified lncRNA-SNHG8 binds to PTBP1 to regulate ALAS2 expression to increase oxidative stress and promote myocardial infarction. Molecular and cellular biochemistry 36 36282350
2022 LncRNA SFTA1P promotes cervical cancer progression by interaction with PTBP1 to facilitate TPM4 mRNA degradation. Cell death & disease 36 36344495
2023 Capture RIC-seq reveals positional rules of PTBP1-associated RNA loops in splicing regulation. Molecular cell 35 36958328
2022 N6-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1/HuR complex. Cell death and differentiation 35 35871232
2020 The Emerging Role of the RBM20 and PTBP1 Ribonucleoproteins in Heart Development and Cardiovascular Diseases. Genes 34 32276354
2022 PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics 33 35664063
2021 MicroRNA‑133b alleviates doxorubicin‑induced cardiomyocyte apoptosis and cardiac fibrosis by targeting PTBP1 and TAGLN2. International journal of molecular medicine 33 33982775
2018 PTBP1 promotes tumorigenesis by regulating apoptosis and cell cycle in colon cancer. Bulletin du cancer 33 30309622
2019 Long noncoding RNA HCG22 suppresses proliferation and metastasis of bladder cancer cells by regulation of PTBP1. Journal of cellular physiology 32 31304601
2023 The PTBP1‑NCOA4 axis promotes ferroptosis in liver cancer cells. Oncology reports 28 36660932
2023 The role of RNA splicing factor PTBP1 in neuronal development. Biochimica et biophysica acta. Molecular cell research 28 37263298
2009 hnRNP I inhibits Notch signaling and regulates intestinal epithelial homeostasis in the zebrafish. PLoS genetics 28 19197356
2024 LncRNA DCRT Protects Against Dilated Cardiomyopathy by Preventing NDUFS2 Alternative Splicing by Binding to PTBP1. Circulation 27 38841852
2021 Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer. International journal of cancer 27 34346508
2018 PTBP1 enhances miR-101-guided AGO2 targeting to MCL1 and promotes miR-101-induced apoptosis. Cell death & disease 27 29748555
2018 Post-Translational Modifications in Polypyrimidine Tract Binding Proteins PTBP1 and PTBP2. Biochemistry 27 29851470
2023 PTBP1 as a potential regulator of disease. Molecular and cellular biochemistry 26 38129625
2023 PTBP1-activated co-transcriptional splicing controls epigenetic status of pluripotent stem cells. Molecular cell 25 36626906
2021 LncRNA HOTTIP facilitates cell proliferation, invasion, and migration in osteosarcoma by interaction with PTBP1 to promote KHSRP level. Cell cycle (Georgetown, Tex.) 25 33475442
1997 Sequence determinants for hnRNP I protein nuclear localization. Experimental cell research 25 9281380
2022 Splice factor polypyrimidine tract-binding protein 1 (Ptbp1) primes endothelial inflammation in atherogenic disturbed flow conditions. Proceedings of the National Academy of Sciences of the United States of America 24 35858420
2019 RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production. International immunology 24 30476084
2023 Integrative solution structure of PTBP1-IRES complex reveals strong compaction and ordering with residual conformational flexibility. Nature communications 23 37833274
2017 hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer. PLoS genetics 23 28296893
2024 M6A-modified lncRNA FAM83H-AS1 promotes colorectal cancer progression through PTBP1. Cancer letters 22 38964733
2021 PTBP1 is necessary for dendritic cells to regulate T-cell homeostasis and antitumour immunity. Immunology 22 33421118
2020 LncRNA-Malat1 is Involved in Lipotoxicity-Induced ß-cell Dysfunction and the Therapeutic Effect of Exendin-4 via Ptbp1. Endocrinology 22 32324218
2012 Polypyrimidine tract binding protein (hnRNP I) is possibly a conserved modulator of miRNA-mediated gene regulation. PloS one 22 22427970
2024 Artesunate alleviates sepsis-induced liver injury by regulating macrophage polarization via the lncRNA MALAT1/PTBP1/IFIH1 axis. Diagnostic microbiology and infectious disease 21 38889486
2023 PTBP1 drives c-Myc-dependent gastric cancer progression and stemness. British journal of cancer 21 36635500
2018 RNA-binding proteins RBM20 and PTBP1 regulate the alternative splicing of FHOD3. The international journal of biochemistry & cell biology 21 30468920
2000 Organization of the human gene encoding heterogeneous nuclear ribonucleoprotein type I (hnRNP I) and characterization of hnRNP I related pseudogene. Gene 21 11024286
2024 PTBP1 crotonylation promotes colorectal cancer progression through alternative splicing-mediated upregulation of the PKM2 gene. Journal of translational medicine 20 39497094
2023 Therapeutic Potential of PTBP1 Inhibition, If Any, Is Not Attributed to Glia-to-Neuron Conversion. Annual review of neuroscience 19 36750409
2023 PTBP1 regulates injury responses and sensory pathways in adult peripheral neurons. Science advances 18 37506203
2022 Polypyrimidine tract binding proteins PTBP1 and PTBP2 interact with distinct proteins under splicing conditions. PloS one 18 35113929
2023 PTBP1 suppresses porcine epidemic diarrhea virus replication via inducing protein degradation and IFN production. The Journal of biological chemistry 17 37392846
2022 Deubiquitinating enzyme PSMD14 facilitates gastric carcinogenesis through stabilizing PTBP1. Experimental cell research 17 35405117
2020 Long non-coding RNA SNHG1 regulates rheumatoid synovial invasion and proliferation by interaction with PTBP1. International immunopharmacology 17 33218941
2015 Ptbp1 and Exosc9 knockdowns trigger skin stability defects through different pathways. Developmental biology 17 26546114
2024 USP46 enhances tamoxifen resistance in breast cancer cells by stabilizing PTBP1 to facilitate glycolysis. Biochimica et biophysica acta. Molecular basis of disease 16 38176460
2024 PTBP1 Regulates DNMT3B Alternative Splicing by Interacting With RALY to Enhance the Radioresistance of Prostate Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 39287090
2016 Identification of neural stem cell differentiation repressor complex Pnky-PTBP1. Stem cell investigation 16 27358902
2023 Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota-HIF1a/PTBP1 pathway. Experimental & molecular medicine 15 38036735
2024 circEPB41L2 blocks the progression and metastasis in non-small cell lung cancer by promoting TRIP12-triggered PTBP1 ubiquitylation. Cell death discovery 14 38341427
2024 PTBP1-mediated biogenesis of circATIC promotes progression and cisplatin resistance of bladder cancer. International journal of biological sciences 14 38993556
2024 PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress. Cellular & molecular biology letters 14 39153986
2023 The lncRNA MIR99AHG directs alternative splicing of SMARCA1 by PTBP1 to enable invadopodia formation in colorectal cancer cells. Science signaling 14 37725664
2022 The latest role of nerve-specific splicing factor PTBP1 in the transdifferentiation of glial cells into neurons. Wiley interdisciplinary reviews. RNA 14 35574699
2022 circEXOC5 promotes acute lung injury through the PTBP1/Skp2/Runx2 axis to activate autophagy. Life science alliance 14 36302650
2018 PTBP1 contributes to spermatogenesis through regulation of proliferation in spermatogonia. The Journal of reproduction and development 14 30416150
2024 Exosomes containing circSCP2 in colorectal cancer promote metastasis via sponging miR-92a-1-5p and interacting with PTBP1 to stabilize IGF2BP1. Biology direct 13 39702234
2023 Endothelial deletion of PTBP1 disrupts ventricular chamber development. Nature communications 13 37002228
2017 Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction. Frontiers in molecular neuroscience 13 28553201
2025 SLC7A5/E2F1/PTBP1/PKM2 axis mediates progression and therapy effect of triple-negative breast cancer through the crosstalk of amino acid metabolism and glycolysis pathway. Cancer letters 12 40054655
2024 Regulation of Ptbp1-controlled alternative splicing of pyruvate kinase muscle by liver kinase B1 governs vascular smooth muscle cell plasticity in vivo. Cardiovascular research 12 39189621
2023 hnRNPH1 establishes Sertoli-germ cell crosstalk through cooperation with PTBP1 and AR, and is essential for male fertility in mice. Development (Cambridge, England) 12 36718792
2022 PTBP1 promotes hematopoietic stem cell maintenance and red blood cell development by ensuring sufficient availability of ribosomal constituents. Cell reports 12 35545054
2022 RETRACTED: HOXA11-AS1 Promotes PD-L1-Mediated Immune Escape and Metastasis of Hypopharyngeal Carcinoma by Facilitating PTBP1 and FOSL1 Association. Cancers 12 35954358
2023 Lactobacillus rhamnosus GG ameliorates radiation-induced lung fibrosis via lncRNASNHG17/PTBP1/NICD axis modulation. Biology direct 11 36635762
2022 LncRNA ROR promotes NLRP3-mediated cardiomyocyte pyroptosis by upregulating FOXP1 via interactions with PTBP1. Cytokine 11 35180562
2022 Long noncoding RNA LBX2-AS1 promotes colorectal cancer progression via binding with PTBP1 and stabilizing KAT2A expression. Journal of biochemical and molecular toxicology 11 35253306
2016 Insights into the Regulation of mRNA Processing of Polycistronic Transcripts Mediated by DRBD4/PTB2, a Trypanosome Homolog of the Polypyrimidine Tract-Binding Protein. The Journal of eukaryotic microbiology 11 26663092
2024 Suppression of PTBP1 in hippocampal astrocytes promotes neurogenesis and ameliorates recognition memory in mice with cerebral ischemia. Scientific reports 10 39227632

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