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pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing. Here, we show that the conserved U6 snRNA m6A methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of METT-10 in C. elegans and METTL16 in humans primarily leads to alternative splicing at 5' splice sites with an adenosine at +4 position. In addition, METT-10 is required for splicing of weak 3' cis- and trans-splice sites. We identified a significant overlap between METT-10 and the conserved splicing factor SNRNP27K in regulating 5' splice sites with +4A. Finally, we show that editing endogenous 5' splice site +4A positions to +4U restores splicing to wild-type positions in a mett-10 mutant background, supporting a direct role for U6 snRNA m6A modification in 5' splice site recognition. We conclude that the U6 snRNA m6A modification is important for accurate and efficient pre-mRNA splicing.
Pubmed ID: 38808663
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Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsA Python-based environment of open-source software for mathematics, science, and engineering. The core packages of SciPy include: NumPy, a base N-dimensional array package; SciPy Library, a fundamental library for scientific computing; and IPython, an enhanced interactive console.
View all literature mentionsPython 2D plotting library which produces publication quality figures in variety of hardcopy formats and interactive environments across platforms. Used in python scripts, web application servers, and six graphical user interface toolkits. Used to generate plots, histograms, power spectra, bar charts, error charts, scatter plots.
View all literature mentionsCaenorhabditis elegans with name C. elegans wild type (ancestral). from WB.
View all literature mentionsCenter that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
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