Nature communications, 2021-11, Vol.12 (1), p.6648-6648, Article 6648
2021
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- Autor(en) / Beteiligte
- Titel
- DHX15-independent roles for TFIP11 in U6 snRNA modification, U4/U6.U5 tri-snRNP assembly and pre-mRNA splicing fidelity
- Ist Teil von
- Nature communications, 2021-11, Vol.12 (1), p.6648-6648, Article 6648
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The U6 snRNA, the core catalytic component of the spliceosome, is extensively modified post-transcriptionally, with 2’-O-methylation being most common. However, how U6 2’-O-methylation is regulated remains largely unknown. Here we report that TFIP11, the human homolog of the yeast spliceosome disassembly factor Ntr1, localizes to nucleoli and Cajal Bodies and is essential for the 2’-O-methylation of U6. Mechanistically, we demonstrate that TFIP11 knockdown reduces the association of U6 snRNA with fibrillarin and associated snoRNAs, therefore altering U6 2′-O-methylation. We show U6 snRNA hypomethylation is associated with changes in assembly of the U4/U6.U5 tri-snRNP leading to defects in spliceosome assembly and alterations in splicing fidelity. Strikingly, this function of TFIP11 is independent of the RNA helicase DHX15, its known partner in yeast. In sum, our study demonstrates an unrecognized function for TFIP11 in U6 snRNP modification and U4/U6.U5 tri-snRNP assembly, identifying TFIP11 as a critical spliceosome assembly regulator. In yeast, TFIP11 and DHX15 promote the disassembly of spliceosome complex after splicing is completed. Here the authors show that human TFIP11 functions independently of DHX15 and is required for U6 snRNA 2’-O-methylation and U4/U6.U5 tri-snRNP assembly.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-26932-2Titel-ID: cdi_doaj_primary_oai_doaj_org_article_93d4369760d94698a2204e30cd575392
- Format
- –
- Schlagworte
- 101/28, 14/19, 38/77, 38/89, 38/91, 45/29, 45/90, 49/109, 49/31, 631/337/1645, 631/337/384, 631/45/500, 82/80, Accuracy, Biosynthesis, Cajal bodies, Cancer, Cell Nucleolus - metabolism, Cell Survival, Cellular Biology, Coiled Bodies - metabolism, Dismantling, DNA helicase, Fibrillarin, Fidelity, Gene expression, HeLa Cells, Homology, Human health sciences, Humanities and Social Sciences, Humans, Laboratories, Life Sciences, Localization, Methylation, Microscopy, Mitosis, Molecular biology, multidisciplinary, Nuclear Proteins - metabolism, Nuclear Speckles - metabolism, Nucleoli, Oncologie, Oncology, Post-transcription, Protein Binding, Protein Stability, Proteins, Ribonucleoprotein, U4-U6 Small Nuclear - metabolism, Ribonucleoprotein, U5 Small Nuclear - metabolism, Ribonucleoproteins (small nuclear), RNA helicase, RNA Precursors - metabolism, RNA Splicing - physiology, RNA Splicing Factors - genetics, RNA Splicing Factors - metabolism, RNA, Small Nuclear - metabolism, RNA, Small Nucleolar - metabolism, Science, Science (multidisciplinary), Sciences de la santé humaine, snRNA, Spliceosomes - metabolism, Splicing, Subcellular Processes, Yeast, Yeasts