U6 snRNA m6A modification is required for accurate and efficient cis- and trans-splicing of C. elegans mRNAs.
U6 snRNA m6A modification is required for accurate and efficient cis- and trans-splicing of C. elegans mRNAs.
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U6 snRNA m6A 修饰是线虫 mRNA 准确有效的顺式和反式剪接所必需的。
DOI：
10.1101/2023.09.16.558044
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Akay,Alper
中科院分区：
文献类型：
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作者：
Shen,Aykut;Hencel,Katarzyna;Parker,MatthewT;Scott,Robyn;Skukan,Roberta;Adesina,AduragbemiS;Metheringham,CareyL;Miska,EricA;Nam,Yunsun;Haerty,Wilfried;Simpson,GordonG;Akay,Alper
前mRNA剪接是真核基因表达的关键特征。许多真核生物使用顺式剪接从前mRNA中去除内含子序列。除了顺式剪接外，许多生物体还使用反式剪接将mRNA的5′端替换为非编码剪接前导RNA。顺式和反式剪接都依赖于剪接体U snRNA和相关蛋白质准确识别剪接位点序列。剪接体snRNA携带多种RNA修饰，可能影响前体mRNA剪接的不同阶段。在这里，我们表明，通过RNA甲基转移酶METT-10对U6 snRNA A43的m6 A修饰是准确和有效的C顺式和反式剪接所必需的。线虫前体mRNA。U6 snRNA m6 A修饰的缺失主要导致5′剪接位点的选择性剪接。此外，未修饰的U6 snRNA A43对5′剪接位点的较弱识别影响3′剪接位点的剪接。U6 snRNA m6 A43和剪接因子SNRNP 27 K的功能是识别一组重叠的5′剪接位点，其+4位有一个腺苷。最后，我们证明了U6 snRNA m6 A43是在弱3′反式剪接位点进行有效SL反式剪接所必需的。我们的结论是，U6 snRNA m6 A修饰是重要的准确和有效的顺式和反式剪接在C。优美的
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.