ArticlePLoS genetics2013
The conserved intronic cleavage and polyadenylation site of CstF-77 gene imparts control of 3' end processing activity through feedback autoregulation and by U1 snRNP.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 50 citations in OpenAlex.
- Spatially resolved mNature methods · 2026Article
- Regulation of gene expression by alternative polyadenylation in health and disease.Nature reviews. Genetics · 2026Review
- Alternative polyadenylation releases PCBP1-mediated suppression of CFIm25 during macrophage differentiation.FEBS letters · 2026Article
- Modulating the cleavage and polyadenylation site: from research tools to therapeutic opportunities.RNA (New York, N.Y.) · 2026Review
- RBBP6 anchors pre-mRNA 3' end processing to nuclear speckles for efficient gene expression.Molecular cell · 2025Article
- CSTF3 contributes to platinum resistance in ovarian cancer through alternative polyadenylation of lncRNA NEAT1 and generating the short isoform NEAT1_1.Cell death & disease · 2024Article
- Deep learning of human polyadenylation sites at nucleotide resolution reveals molecular determinants of site usage and relevance in disease.Nature communications · 2023Article
- RNA polymerase II transcription attenuation at the yeast DNA repair gene DEF1 is biologically significant and dependent on the Hrp1 RNA-recognition motif.G3 (Bethesda, Md.) · 2023Article
- Article
- Context-specific regulation and function of mRNA alternative polyadenylation.Nature reviews. Molecular cell biology · 2022Review
- CYCLIN K down-regulation induces androgen receptor gene intronic polyadenylation, variant expression and PARP inhibitor vulnerability in castration-resistant prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- CRISPRpas: programmable regulation of alternative polyadenylation by dCas9.Nucleic acids research · 2022Article
- Article
- Regulation of the Alternative Neural Transcriptome by ELAV/Hu RNA Binding Proteins.Frontiers in genetics · 2022Review
- RNA Modifications and RNA Metabolism in Neurological Disease Pathogenesis.International journal of molecular sciences · 2021Review
- Alternative polyadenylation: methods, mechanism, function, and role in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Requirement for cleavage factor IIRNA (New York, N.Y.) · 2020Article
- Plant 3' Regulatory Regions From mRNA-Encoding Genes and Their Uses to Modulate Expression.Frontiers in plant science · 2020Review
- Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability.Nature communications · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The human gene encoding the cleavage/polyadenylation (C/P) factor CstF-77 contains 21 exons. However, intron 3 (In3) accounts for nearly half of the gene region, and contains a C/P site (pA) with medium strength, leading to short mRNA isoforms with no apparent protein products. This intron contains a weak 5' splice site (5'SS), opposite to the general trend for large introns in the human genome. Importantly, the intron size and strengths of 5'SS and pA are all highly conserved across vertebrates, and perturbation of these parameters drastically alters intronic C/P. We found that the usage of In3 pA is responsive to the expression level of CstF-77 as well as several other C/P factors, indicating it attenuates the expression of CstF-77 via a negative feedback mechanism. Significantly, intronic C/P of CstF-77 pre-mRNA correlates with global 3'UTR length across cells and tissues. In addition, inhibition of U1 snRNP also leads to regulation of the usage of In3 pA, suggesting that the C/P activity in the cell can be cross-regulated by splicing, leading to coordination between these two processes. Importantly, perturbation of CstF-77 expression leads to widespread alternative cleavage and polyadenylation (APA) and disturbance of cell proliferation and differentiation. Thus, the conserved intronic pA of the CstF-77 gene may function as a sensor for cellular C/P and splicing activities, controlling the homeostasis of CstF-77 and C/P activity and impacting cell proliferation and differentiation.
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