Spliceosomal proteins direct RNA methylation to modulate gene expression and silence retrotransposons
- 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
2026-07-08
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.