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Spliceosomal proteins direct RNA methylation to modulate gene expression and silence retrotransposons [ChIP-seq]

ABSTRACT: RNA modifications play indispensable roles in RNA processing and gene regulation, but the mechanistic diversity and transcript specificity of RNA-modifying activities remain unclear. Using genetic screening and biochemical analyses in S. pombe, we identified the RNA methyltransferase Tgs1 as a component of a protein complex called TEaM, which is specifically recruited by spliceosomal proteins to transcripts containing inefficiently spliced cryptic introns. Strikingly, the presence of cryptic introns alone can trigger TEaM-dependent silencing of stress-inducible genes and repetitive elements, including retrotransposons, while Tgs1 is also directed to gametogenic transcripts via a YTH-domain RNA-binding protein. In both contexts, Tgs1 catalyzes trimethylguanosine (TMG) capping, a modification that recruits the conserved Pir2/ARS2 protein and promotes RNA processing through the RNAi pathway. Our findings uncover how splicing machinery and YTH proteins converge on a common regulatory mechanism—TMG capping—that facilitates RNAi-mediated silencing via Pir2/ARS2, providing new insights into gene silencing pathways across eukaryotic species.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE300775 | GEO | 2026/06/25

REPOSITORIES: GEO

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Spliceosomal proteins direct RNA methylation to modulate gene expression and silence retrotransposons [RIP-seq]

Project description:RNA modifications play indispensable roles in RNA processing and gene regulation, but the mechanistic diversity and transcript specificity of RNA-modifying activities remain unclear. Using genetic screening and biochemical analyses in S. pombe, we identified the RNA methyltransferase Tgs1 as a component of a protein complex called TEaM, which is specifically recruited by spliceosomal proteins to transcripts containing inefficiently spliced cryptic introns. Strikingly, the presence of cryptic introns alone can trigger TEaM-dependent silencing of stress-inducible genes and repetitive elements, including retrotransposons, while Tgs1 is also directed to gametogenic transcripts via a YTH-domain RNA-binding protein. In both contexts, Tgs1 catalyzes trimethylguanosine (TMG) capping, a modification that recruits the conserved Pir2/ARS2 protein and promotes RNA processing through the RNAi pathway. Our findings uncover how splicing machinery and YTH proteins converge on a common regulatory mechanism—TMG capping—that facilitates RNAi-mediated silencing via Pir2/ARS2, providing new insights into gene silencing pathways across eukaryotic species.

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Cryptic introns in lncRNAs recruit conserved Pir2/ARS2 protein to promote gene repression [ChIP-seq]

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Project description:Cryptic introns in lncRNAs recruit conserved Pir2/ARS2 protein to promote gene repression

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