ArticleGenes & development2010
The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 214 citations in OpenAlex.
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- Lactate derived from cancer-associated fibroblasts promotes alternative splicing and castration resistance in prostate cancer.Science advances · 2026Article
- A Stable Bioisostere of Ester-Linked Ubiquitin Chains Enables Decoding of Protein Interactors.Chembiochem : a European journal of chemical biology · 2026Article
- Light regulates nuclear detainment of intron-retained transcripts through COP1-spliceosome to modulate photomorphogenesis.Nature communications · 2024Article
- Improved detection of DNA replication fork-associated proteins.Cell reports · 2024Article
- The deubiquitinating enzyme USP4 regulates BRCA1 stability and function.NPJ breast cancer · 2024Article
- TRIM25 promotes glioblastoma cell growth and invasion via regulation of the PRMT1/c-MYC pathway by targeting the splicing factor NONO.Journal of experimental & clinical cancer research : CR · 2024Article
- Diverse roles of UBE2S in cancer and therapy resistance: Biological functions and mechanisms.Heliyon · 2024Review
- Crosstalk between ubiquitination and translation in neurodevelopmental disorders.Frontiers in molecular neuroscience · 2024Review
- LncRNAPNAS nexus · 2023Article
- Genes of the Ubiquitin Proteasome System Qualify as Differential Markers in Malignant Glioma of Astrocytic and Oligodendroglial Origin.Cellular and molecular neurobiology · 2023Review
- Regulation of Pre-mRNA Splicing: Indispensable Role of Post-Translational Modifications of Splicing Factors.Life (Basel, Switzerland) · 2023Review
- An atlas of posttranslational modifications on RNA binding proteins.Nucleic acids research · 2022Article
- The PRP19 Ubiquitin Ligase, Standing at the Cross-Roads of mRNA Processing and Genome Stability.Cancers · 2022Review
- USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1.Cell death discovery · 2022Article
- LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.The Journal of cell biology · 2022Article
- Ubiquitination and Ubiquitin-Like Modifications as Mediators of Alternative Pre-mRNA Splicing inFrontiers in plant science · 2022Review
- Insights Into the Properties, Biological Functions, and Regulation of USP21.Frontiers in pharmacology · 2022Review
80 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The spliceosome, a dynamic assembly of proteins and RNAs, catalyzes the excision of intron sequences from nascent mRNAs. Recent work has suggested that the activity and composition of the spliceosome are regulated by ubiquitination, but the underlying mechanisms have not been elucidated. Here, we report that the spliceosomal Prp19 complex modifies Prp3, a component of the U4 snRNP, with nonproteolytic K63-linked ubiquitin chains. The K63-linked chains increase the affinity of Prp3 for the U5 snRNP component Prp8, thereby allowing for the stabilization of the U4/U6.U5 snRNP. Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site. Loss of Usp4 in cells interferes with the accumulation of correctly spliced mRNAs, including those for alpha-tubulin and Bub1, and impairs cell cycle progression. We propose that the reversible ubiquitination of spliceosomal proteins, such as Prp3, guides rearrangements in the composition of the spliceosome at distinct steps of the splicing reaction.
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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.