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<p>RNA modifications are fundamental to gene regulation and RNA processing, yet their diversity and transcript specificity remain incompletely defined. Here, using a genetic screen in&#xa0;<i>S.&#xa0;pombe</i>, we identify the RNA methyltransferase Tgs1 and Coilin-related proteins as regulators of transcripts harboring inefficiently spliced cryptic introns. These factors associate to form a protein assembly, termed TEaM, which is recruited to cryptic-intron-containing RNAs, including retrotransposon-derived transcripts, by spliceosomal components, and to gametogenic gene transcripts by a YTH-family RNA-binding protein. Upon recruitment, Tgs1 catalyzes trimethylguanosine (TMG) capping, facilitating engagement of the conserved factor Pir2/ARS2, which cooperates with the DROSHA homolog Pac1 and other factors to promote RNA processing and RNAi-mediated silencing. This pathway also targets centromeric repeat RNAs containing cryptic introns, enabling de novo&#xa0;production of siRNAs that specify heterochromatin nucleation. Together, these findings delineate a mechanism in which Tgs1-directed TMG capping, coupled with Pir2/ARS2, specifies RNAi substrates to broadly regulate gene expression and silence retrotransposons.</p>

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Spliceosomal proteins direct RNA methylation to modulate gene expression and silence retrotransposons

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Drisya Vijayakumari,
  • Xander Gottfried,
  • Brent Groubert,
  • Jothy Dhakshnamoorthy,
  • Shweta Jain,
  • Martin Zofall,
  • Hernan Diego Folco,
  • Hua Xiao,
  • Anupa T Anil,
  • Thorkell Andresson,
  • David Wheeler,
  • Shiv I. S. Grewal

摘要

RNA modifications are fundamental to gene regulation and RNA processing, yet their diversity and transcript specificity remain incompletely defined. Here, using a genetic screen in S. pombe, we identify the RNA methyltransferase Tgs1 and Coilin-related proteins as regulators of transcripts harboring inefficiently spliced cryptic introns. These factors associate to form a protein assembly, termed TEaM, which is recruited to cryptic-intron-containing RNAs, including retrotransposon-derived transcripts, by spliceosomal components, and to gametogenic gene transcripts by a YTH-family RNA-binding protein. Upon recruitment, Tgs1 catalyzes trimethylguanosine (TMG) capping, facilitating engagement of the conserved factor Pir2/ARS2, which cooperates with the DROSHA homolog Pac1 and other factors to promote RNA processing and RNAi-mediated silencing. This pathway also targets centromeric repeat RNAs containing cryptic introns, enabling de novo production of siRNAs that specify heterochromatin nucleation. Together, these findings delineate a mechanism in which Tgs1-directed TMG capping, coupled with Pir2/ARS2, specifies RNAi substrates to broadly regulate gene expression and silence retrotransposons.