ArticleNucleic acids research2019
Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6.
Article in Nucleic acids research, 2019. 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, 55 citations in OpenAlex.
- Multiple roads between the nucleus and the cytoplasm: classes of linear NLSs and NESs and their receptors.Current opinion in structural biology · 2026Review
- Bridging sequence-structure motifs and genetic variants for genome-wide dynamic RNA-protein interaction profiling.Nature communications · 2026Article
- Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6.International journal of molecular sciences · 2026Review
- IGF2BP2 binding to CPSF6 facilitates m6A-mediated alternative polyadenylation of PUM2 and promotes malignant progression in ovarian cancer.Clinical and translational medicine · 2025Article
- Molecular Imprints of Clinical Comorbidities in Hypothalamic Extracellular Vesicles at the Onset of Obesity.ACS omega · 2025Article
- CPSF6 promotes HIV-1 preintegration complex function.Journal of virology · 2025Article
- Structural basis of phosphorylation-independent nuclear import of CIRBP by TNPO3.Nature communications · 2025Article
- Phosphate-dependent nuclear export via a non-classical NES class recognized by exportin Msn5.Nature communications · 2025Article
- Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025Review
- The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.PLoS pathogens · 2025Article
- HIV-1 usurps mixed-charge domain-dependent CPSF6 phase separation for higher-order capsid binding, nuclear entry and viral DNA integration.Nucleic acids research · 2024Article
- HIV-1-induced translocation of CPSF6 to biomolecular condensates.Trends in microbiology · 2024Review
- The nuclear localization signal of CPSF6 governs post-nuclear import steps of HIV-1 infection.bioRxiv : the preprint server for biology · 2024Article
- Review
- Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration.bioRxiv : the preprint server for biology · 2024Article
- Downregulation of CPSF6 leads to global mRNA 3' UTR shortening and enhanced antiviral immune responses.PLoS pathogens · 2024Article
- Alternative Polyadenylation Regulatory Factors Signature for Survival Prediction in Kidney Renal Cell Carcinoma.Cancer informatics · 2024Article
- Capsid-host interactions for HIV-1 ingress.Microbiology and molecular biology reviews : MMBR · 2023Review
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- Mislocalization of pathogenic RBM20 variants in dilated cardiomyopathy is caused by loss-of-interaction with Transportin-3.Nature communications · 2023Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor 5 (CPSF5) and serine/arginine-like protein CPSF6, regulates alternative polyadenylation (APA). Loss of CFIm function results in proximal polyadenylation site usage, shortening mRNA 3' untranslated regions (UTRs). Although CPSF6 plays additional roles in human disease, its nuclear translocation mechanism remains unresolved. Two β-karyopherins, transportin (TNPO) 1 and TNPO3, can bind CPSF6 in vitro, and we demonstrate here that while the TNPO1 binding site is dispensable for CPSF6 nuclear import, the arginine/serine (RS)-like domain (RSLD) that mediates TNPO3 binding is critical. The crystal structure of the RSLD-TNPO3 complex revealed potential CPSF6 interaction residues, which were confirmed to mediate TNPO3 binding and CPSF6 nuclear import. Both binding and nuclear import were independent of RSLD phosphorylation, though a hyperphosphorylated mimetic mutant failed to bind TNPO3 and mislocalized to the cell cytoplasm. Although hypophosphorylated CPSF6 largely supported normal polyadenylation site usage, a significant number of mRNAs harbored unnaturally extended 3' UTRs, similar to what is observed when other APA regulators, such as CFIIm component proteins, are depleted. Our results clarify the mechanism of CPSF6 nuclear import and highlight differential roles for RSLD phosphorylation in nuclear translocation versus regulation of APA.
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