U6 snRNA m6A modification is required for accurate and efficient cis- and trans-splicing of C. elegans mRNAs.

Autor:	Shen A; School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich., Hencel K; School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich.; These authors contributed equally., Parker MT; School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.; These authors contributed equally., Scott R; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA., Skukan R; School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich., Adesina AS; School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich., Metheringham CL; School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK., Miska EA; Wellcome/CRUK Gurdon Institute, University of Cambridge, Tennis Court Rd, Cambridge, CB2 1QN, UK., Nam Y; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA., Haerty W; School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich.; Earlham Institute, Norwich Research Park, Norwich, UK., Simpson GG; School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.; Cell & Molecular Sciences, James Hutton Institute, Invergowrie, DD2 5DA, UK., Akay A; School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 16. Date of Electronic Publication: 2023 Sep 16.
DOI:	10.1101/2023.09.16.558044
Abstrakt:	pre-mRNA splicing is a critical feature of eukaryotic gene expression. Many eukaryotes use cis-splicing to remove intronic sequences from pre-mRNAs. In addition to cis-splicing, many organisms use trans-splicing to replace the 5' ends of mRNAs with a non-coding spliced-leader RNA. 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 m6A modification of U6 snRNA A43 by the RNA methyltransferase METT-10 is required for accurate and efficient cis- and trans-splicing of C. elegans pre-mRNAs. The absence of U6 snRNA m6A modification primarily leads to alternative splicing at 5' splice sites. Furthermore, weaker 5' splice site recognition by the unmodified U6 snRNA A43 affects splicing at 3' splice sites. U6 snRNA m6A43 and the splicing factor SNRNP27K function to recognise an overlapping set of 5' splice sites with an adenosine at +4 position. Finally, we show that U6 snRNA m6A43 is required for efficient SL trans-splicing at weak 3' trans-splice sites. We conclude that the U6 snRNA m6A modification is important for accurate and efficient cis- and trans-splicing in C. elegans .
Databáze:	MEDLINE
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