Affinage

LUC7L

Putative RNA-binding protein Luc7-like 1 · UniProt Q9NQ29

Round 2 corrected
Length
371 aa
Mass
43.7 kDa
Annotated
2026-04-28
44 papers in source corpus 7 papers cited in narrative 8 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LUC7L is a U1 snRNP-associated splicing factor that, together with its paralogs LUC7L2 and LUC7L3, promotes recognition of 5' splice sites during pre-mRNA splicing, with LUC7L and LUC7L2 preferentially enhancing splicing of 'right-handed' 5' splice sites (stronger consensus on the intron side of the /GU dinucleotide) (PMID:39979239). Its second zinc finger domain (ZnF2) is essential for splice-site selection and modulates the ATPase requirement for U1 snRNP release, whereas ZnF1 is dispensable under standard conditions (PMID:27354704, PMID:38719745). Each human LUC7 paralog binds a shared core set of splicing factors but recruits distinct regulatory splicing factors through its divergent RS domain and regulates largely non-overlapping alternative splicing events (PMID:33852859). LUC7L localizes to nuclear speckles via its RS domain, and its downregulation during skeletal muscle differentiation is functionally linked to myogenesis, as forced overexpression inhibits myoblast differentiation (PMID:15474286).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2001 Medium

    Identifying LUC7L as a human homolog of yeast Luc7p established it as a candidate U1 snRNP-associated splicing factor and raised the question of whether it conserves 5' splice site selection function.

    Evidence Genomic mapping and sequence homology analysis at 16p13.3

    PMID:11170747

    Open questions at the time
    • No functional assay performed
    • Homology alone does not confirm splicing function
    • No protein-level characterization
  2. 2004 Medium

    Demonstrating that murine Luc7l localizes to nuclear speckles via its RS domain and that its overexpression blocks myogenesis provided the first evidence that LUC7L has biological function beyond splicing catalysis.

    Evidence Subcellular imaging and forced overexpression in Sol8/C2C12 myoblast differentiation assays

    PMID:15474286

    Open questions at the time
    • Mechanism of myogenesis inhibition unknown (direct splicing target vs. indirect)
    • Single-lab result not replicated independently
    • Loss-of-function during differentiation not tested
  3. 2008 Medium

    Mapping the physical interaction between yeast Luc7p and Prp40 via a defined binding motif within a U1 snRNP subcomplex (Luc7–Snu71–Prp40) clarified how Luc7 is tethered within the U1 particle.

    Evidence Yeast two-hybrid and GST pulldown with peptide-level mapping in yeast

    PMID:19014439

    Open questions at the time
    • Whether the same binding mode operates for human LUC7L–PRPF40A was untested
    • Structural detail of the subcomplex lacking
    • Functional consequence of disrupting this interaction on splicing not shown
  4. 2016 High

    Systematic mutagenesis of yeast Luc7 established that ZnF2 is essential for viability and nonconsensus 5' splice site usage, while the N-terminal segment stabilizes U1 snRNP interactions and genetically links Luc7 to the DEAD-box ATPase Prp28.

    Evidence Alanine-scanning mutagenesis, truncation analysis, synthetic lethality screens, and pre-mRNA splicing assays in yeast

    PMID:27354704

    Open questions at the time
    • Human LUC7L domain functions not directly tested
    • Structural basis of ZnF2–RNA interaction unknown
    • Role of ZnF1 remained enigmatic
  5. 2021 High

    Demonstrating that the three human LUC7 paralogs share a core splicing-factor interactome but bind distinct regulatory factors through their divergent RS domains, and regulate largely non-overlapping alternative splicing events, resolved how paralog-specific splicing regulation arises.

    Evidence IP-MS, siRNA knockdown with RNA-seq, and CLIP/crosslinking in human cell lines

    PMID:33852859

    Open questions at the time
    • Direct RNA targets of LUC7L (vs. LUC7L2/L3) were less well resolved by CLIP
    • Functional redundancy versus essentiality of individual paralogs not fully addressed
    • Structural basis of RS domain partner selectivity unknown
  6. 2024 High

    Humanizing the ZnF2 domain of yeast Luc7 with human LUC7L or LUC7L2 sequences altered nonconsensus 5' splice site usage and suppressed Prp28 ATPase mutations, directly demonstrating that ZnF2 identity dictates splice-site specificity and U1 snRNP release dynamics.

    Evidence Domain-swap/humanization in yeast with reporter splicing assays, transcriptome analysis, and Prp28 genetic suppression

    PMID:38719745

    Open questions at the time
    • LUC7L3 ZnF2 incompatibility with yeast viability not mechanistically explained
    • Whether ZnF2 contacts RNA directly or acts via protein–protein interactions unresolved
    • Human cellular context not tested
  7. 2025 High

    Establishing that LUC7L/LUC7L2 preferentially enhance 'right-handed' 5' splice sites while LUC7L3 enhances 'left-handed' sites — a distinction conserved from plants to animals — defined the molecular logic underlying paralog-specific splice-site selection.

    Evidence Transcriptomics in human cell lines and leukemias, splice-site mutagenesis, domain swaps between human paralogs, and Arabidopsis LUC7 mutant analysis

    PMID:39979239

    Open questions at the time
    • Structural basis of right- vs. left-handed specificity not determined
    • In vivo phenotypic consequence of LUC7L loss in mammals untested
    • Whether right/left-handed preference is modulated by cellular context unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the direct RNA-binding mode and structural basis of ZnF2-mediated splice-site specificity, the in vivo consequence of LUC7L loss in mammalian development, and the mechanism by which LUC7L overexpression inhibits myogenesis.
  • No mammalian knockout or conditional deletion phenotype reported
  • No high-resolution structure of LUC7L or its domains
  • Homeostatic cross-regulation with PRPF40A awaits peer-reviewed confirmation

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3
Localization
GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 4
Partners
LUC7L2LUC7L3PRPF40A
Complex memberships
U1 snRNP

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 LUC7L was identified as the first gene on the centromeric side of the human alpha-globin cluster on 16p13.3, encoding a putative RNA-binding protein homologous to the yeast U1 snRNP subunit Luc7p, implicated in 5' splice site selection. Genomic mapping, sequence analysis, identification of mouse orthologue on chromosome 17 Genomics Medium 11170747
2004 Murine Luc7l localizes to the nucleus in a speckled distribution pattern mediated by its C-terminal arginine-serine-rich (RS) domain, and forced overexpression of Luc7l inhibits myogenesis in vitro; endogenous Luc7l expression is downregulated during skeletal muscle differentiation. Gene trap identification, subcellular localization imaging, forced overexpression in Sol8 and C2C12 myoblast cell lines with myogenic differentiation assay Gene Medium 15474286
2008 Yeast Luc7p interacts with the first FF domain of Prp40 via a defined binding motif (phi[FHL]x[KR]x[GHL]) within Luc7, and together with Snu71 forms a subcomplex within the U1 snRNP; these interactions were mapped by yeast two-hybrid and GST pulldown assays. Yeast two-hybrid, GST pulldown, peptide array screens BMC biochemistry Medium 19014439
2016 In yeast Luc7, the CCHH zinc finger 2 (ZnF2) motif is essential for viability, while the CCCH zinc finger 1 (ZnF1) and charged residues of ZnF2 are dispensable for vegetative growth but important for splicing of nonconsensus 5' splice sites (e.g., SUS1 pre-mRNA). The N-terminal 18-aa segment of Luc7 stabilizes U1 snRNP interactions and its deletion is synthetically lethal with loss of Mud1, Nam8, TMG cap, or Snp1 C-terminus, and bypasses the requirement for the DEAD-box ATPase Prp28. In vivo alanine-scanning mutagenesis, N/C-terminal truncations, synthetic lethality screens, pre-mRNA splicing assays RNA (New York, N.Y.) High 27354704
2021 All three human LUC7 paralogs (LUC7L, LUC7L2, LUC7L3) bind a similar core set of splicing factors but distinct regulatory splicing factors, mediated through their divergent RS domains absent in yeast Luc7p. Knockdown of each paralog dysregulates largely unique sets of alternative splicing events reflecting their non-overlapping RNA binding locations. LUC7L2 and LUC7L3 crosslink to weak 5' splice sites and to the 5' end of U1 snRNA, establishing a conserved role in 5' splice site selection. Protein interaction studies (immunoprecipitation/MS), siRNA knockdown + RNA-seq, CLIP/crosslinking RNA binding studies Cell reports High 33852859
2024 Humanization of the second zinc finger (ZnF2) domain of yeast Luc7 to mirror the ZnF2 of human LUC7L or LUC7L2 alters usage of nonconsensus 5' splice sites, while the corresponding ZnF2 of LUC7L3 cannot support yeast viability. Humanized Luc7 ZnF2 can suppress mutation of the ATPase Prp28, revealing distinct ATPase requirements for U1 snRNP release. The first ZnF domain had no detectable function in splice site selection under these conditions. Domain-swap/humanization experiments in yeast, reporter splicing assays, transcriptome analysis, genetic interaction (suppression of Prp28 mutation) RNA (New York, N.Y.) High 38719745
2025 LUC7L and LUC7L2 preferentially enhance splicing of 'right-handed' 5' splice sites (stronger consensus on the intron side of the /GU dinucleotide), while LUC7L3 enhances splicing of 'left-handed' 5' splice sites (stronger consensus upstream of /GU). This differential specificity was validated by mutating splice sites and by domain-swapping between human LUC7 paralogs; the LUC7L2/LUC7L3 subfamily distinction predates the animal-plant split. Transcriptome analysis in human cell lines and leukemias with LUC7L2 copy number variation, splice-site mutagenesis, domain-swap experiments between human LUC7 paralogs, analysis of Arabidopsis LUC7 mutants Nature communications High 39979239
2024 Knockdown of PRPF40A (the human ortholog of yeast Prp40, which directly interacts with Luc7) increases productive splicing of LUC7L by skipping of a small 'poison exon,' suggesting homeostatic cross-regulation between the physically and functionally coupled spliceosomal components PRPF40A and LUC7L. PRPF40A knockdown in mouse neuroblastoma cells, RNA-seq analysis of LUC7L splicing isoforms bioRxivpreprint Low

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2011 The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Molecular and cellular biology 437 21555454
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature genetics 406 20139978
2004 A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Molecular cell 339 15383276
2012 Dynamic protein-protein interaction wiring of the human spliceosome. Molecular cell 318 22365833
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2018 Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27 Acetylation. Cell reports 274 30110629
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2011 Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine 180 21653829
2013 The protein interaction landscape of the human CMGC kinase group. Cell reports 174 23602568
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2021 Functional analyses of human LUC7-like proteins involved in splicing regulation and myeloid neoplasms. Cell reports 47 33852859
2018 The U1 snRNP Subunit LUC7 Modulates Plant Development and Stress Responses via Regulation of Alternative Splicing. The Plant cell 41 30309899
2008 The FF domains of yeast U1 snRNP protein Prp40 mediate interactions with Luc7 and Snu71. BMC biochemistry 33 19014439
2001 Characterization of a widely expressed gene (LUC7-LIKE; LUC7L) defining the centromeric boundary of the human alpha-globin domain. Genomics 26 11170747
2016 Structure-function analysis and genetic interactions of the Luc7 subunit of the Saccharomyces cerevisiae U1 snRNP. RNA (New York, N.Y.) 18 27354704
2004 Serine-arginine-rich nuclear protein Luc7l regulates myogenesis in mice. Gene 12 15474286
2025 LUC7 proteins define two major classes of 5' splice sites in animals and plants. Nature communications 8 39979239
2009 Increase in dual specificity phosphatase 1, TGF-beta stimulated gene 22, domain family protein 3 and Luc7 homolog (S. cerevisiae)-like messenger RNA after mechanical asphyxiation in the mouse lung. Legal medicine (Tokyo, Japan) 7 19364672
2024 Functional analysis of the zinc finger modules of the Saccharomyces cerevisiae splicing factor Luc7. RNA (New York, N.Y.) 2 38719745
2024 Circ-Luc7l Absence Attenuates Diabetic Nephropathy Progression by Reducing Mesangial Cell Excessive Proliferation, Inflammation, and Extracellular Matrix Accumulation via Mediating the miR-205-5p/Tgfbr1 Pathway. Biochemical genetics 1 38376578
2014 Fish Myogenic Regulatory Protein LUC7L: Characterization and Expression Analysis in Korean Rose Bitterling (Rhodeus uyekii). Development & reproduction 1 25949195
2025 LUC7L-201 is an important regulator of skeletal muscle growth and development in goats identified through integration of nanopore and Illumina sequencing. Genomics 0 40409693
2024 Functional Analysis of the Zinc Finger Modules of the S. cerevisiae Splicing Factor Luc7. bioRxiv : the preprint server for biology 0 38352541
2018 [Identificación de fármacos reguladores de la actividad del promotor Egr-1 en fibroblastos humanos transducidos con AdΔegr-1-Luc7]. Cirugia y cirujanos 0 29950741