ArticleGenome biology2021
SRSF3 and SRSF7 modulate 3'UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Mechanisms of transcription termination across the coding and noncoding loci of the genome.Nature reviews. Molecular cell biology · 2026Review
- Human-specific sequence features in HTT exon 1 promote toxic misprocessing via splicing factor SRSF7.Nature communications · 2026Article
- HSV ICP27 hijacks host splicing factor SRSF3 to regulate pre-mRNA splicing and export for viral gene expression and immune evasion.PLoS pathogens · 2026Article
- [Expression, Prognostic and Functional Analysis of SRSF Family Proteins in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Multidimensional regulatory roles and therapeutic applications of SRSF7 in cancer.Cell death discovery · 2025Review
- Single-nucleus transcriptome atlas of orbitofrontal cortex in ALS with a deep learning-based decoding of alternative polyadenylation mechanisms.Cell genomics · 2025Article
- Integrative analysis of RNA binding proteins identifies DDX55 as a novel regulator of 3'UTR isoform diversity.Genome biology · 2025Article
- SRSF12 is a primate-specific splicing factor that induces a tissue-specific gene expression program.Molecular biology of the cell · 2025Article
- Rapid depletion and super-resolution microscopy reveal dual roles of SRSF5 in coordinating nuclear speckle-paraspeckle crosstalk during cellular stress.Nucleic acids research · 2025Article
- At-RS31 orchestrates hierarchical cross-regulation of splicing factors and integrates alternative splicing with TOR-ABA pathways.The New phytologist · 2025Article
- SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.Acta pharmaceutica Sinica. B · 2025Article
- C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.Acta neuropathologica communications · 2025Article
- Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression.Molecular oncology · 2025Article
- Fateful Decisions of Where to Cut the Line: Pathology Associated with Aberrant 3' End Processing and Transcription Termination.Journal of molecular biology · 2025Review
- Coupling of alternative splicing and alternative polyadenylation.Acta biochimica et biophysica Sinica · 2024Review
- Systematic identification of post-transcriptional regulatory modules.Nature communications · 2024Article
- Modulation of diverse biological processes by CPSF, the master regulator of mRNA 3' ends.RNA (New York, N.Y.) · 2024Review
- Article
- Arid5a uses disordered extensions of its core ARID domain for distinct DNA- and RNA-recognition and gene regulation.The Journal of biological chemistry · 2024Article
- SR proteins in cancer: function, regulation, and small inhibitor.Cellular & molecular biology letters · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which determines the length of their 3' untranslated regions (3'UTRs). We have recently shown that SRSF3 and SRSF7, two closely related SR proteins, connect APA with mRNA export. The mechanism underlying APA regulation by SRSF3 and SRSF7 remained unknown.
resultsHere we combine iCLIP and 3'-end sequencing and find that SRSF3 and SRSF7 bind upstream of proximal PASs (pPASs), but they exert opposite effects on 3'UTR length. SRSF7 enhances pPAS usage in a concentration-dependent but splicing-independent manner by recruiting the cleavage factor FIP1, generating short 3'UTRs. Protein domains unique to SRSF7, which are absent from SRSF3, contribute to FIP1 recruitment. In contrast, SRSF3 promotes distal PAS (dPAS) usage and hence long 3'UTRs directly by counteracting SRSF7, but also indirectly by maintaining high levels of cleavage factor Im (CFIm) via alternative splicing. Upon SRSF3 depletion, CFIm levels decrease and 3'UTRs are shortened. The indirect SRSF3 targets are particularly sensitive to low CFIm levels, because here CFIm serves a dual function; it enhances dPAS and inhibits pPAS usage by binding immediately downstream and assembling unproductive cleavage complexes, which together promotes long 3'UTRs.
conclusionsWe demonstrate that SRSF3 and SRSF7 are direct modulators of pPAS usage and show how small differences in the domain architecture of SR proteins can confer opposite effects on pPAS regulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.