ArticleProceedings of the National Academy of Sciences of the United States of America2021
CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 36 citations in OpenAlex.
- Evaluating splicing factor and kinase network crosstalk through global phosphoproteomics.bioRxiv : the preprint server for biology · 2026Article
- Transcriptional downregulation of rhodopsin is associated with desensitization of rods to light-induced damage in a murine model of retinitis pigmentosa.Human molecular genetics · 2025Article
- RNA processing kinase inhibitors and epigenetic inhibitors in combination with oncology drugs or investigational agents in multi-cell type patient-derived tumor cell line spheroids.Cancer chemotherapy and pharmacology · 2025Article
- YTHDC1 orchestrates oncogenic splicing via the CLK1-SRSF1 splicing machinery to regulate castration-resistant prostate cancer progression.Molecular and cellular biochemistry · 2025Article
- Swt21p Is Required for Nam8p-U1 snRNP Association and Efficient Pre-mRNA Splicing inInternational journal of molecular sciences · 2025Article
- Evolution and stress response potential of the plant splicing factor U1C.Scientific reports · 2024Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- SRSF5-Mediated Alternative Splicing of M Gene is Essential for Influenza A Virus Replication: A Host-Directed Target Against Influenza Virus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Genome-scale analysis of Arabidopsis splicing-related protein kinase families reveals roles in abiotic stress adaptation.BMC plant biology · 2022Article
- Spliceosomal SL1 RNA binding to U1-70K: the role of the extended RRM.Nucleic acids research · 2022Article
- Cooperative engagement and subsequent selective displacement of SR proteins define the pre-mRNA 3D structural scaffold for early spliceosome assembly.Nucleic acids research · 2022Article
- Plant AFC2 kinase desensitizes thermomorphogenesis through modulation of alternative splicing.iScience · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Early spliceosome assembly requires phosphorylation of U1-70K, a constituent of the U1 small nuclear ribonucleoprotein (snRNP), but it is unclear which sites are phosphorylated, and by what enzyme, and how such modification regulates function. By profiling the proteome, we found that the Cdc2-like kinase 1 (CLK1) phosphorylates Ser-226 in the C terminus of U1-70K. This releases U1-70K from subnuclear granules facilitating interaction with U1 snRNP and the serine-arginine (SR) protein SRSF1, critical steps in establishing the 5' splice site. CLK1 breaks contacts between the C terminus and the RNA recognition motif (RRM) in U1-70K releasing the RRM to bind SRSF1. This reorganization also permits stable interactions between U1-70K and several proteins associated with U1 snRNP. Nuclear induction of the SR protein kinase 1 (SRPK1) facilitates CLK1 dissociation from U1-70K, recycling the kinase for catalysis. These studies demonstrate that CLK1 plays a vital, signal-dependent role in early spliceosomal protein assembly by contouring U1-70K for protein-protein multitasking.
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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 Socratic graph.