An enhancer screen identifies new suppressors of small-RNA-mediated epigenetic gene silencing

Research output: Contribution to journalJournal articleResearchpeer-review

  • Yukiko Shimada
  • Sarah H. Carl
  • Merle Skribbe
  • Flury, Valentin
  • Tahsin Kuzdere
  • Georg Kempf
  • Marc Bühler

Small non-protein coding RNAs are involved in pathways that control the genome at the level of chromatin. In Schizosaccharomyces pombe, small interfering RNAs (siRNAs) are required for the faithful propagation of heterochromatin that is found at peri-centromeric repeats. In contrast to repetitive DNA, protein-coding genes are refractory to siRNA-mediated heterochromatin formation, unless siRNAs are expressed in mutant cells. Here we report the identification of 20 novel mutant alleles that enable de novo formation of heterochromatin at a euchromatic protein-coding gene by using trans-acting siRNAs as triggers. For example, a single amino acid substitution in the pre-mRNA cleavage factor Yth1 enables siRNAs to trigger silent chromatin formation with unparalleled efficiency. Our results are consistent with a kinetic nascent transcript processing model for the inhibition of small-RNA-directed de novo formation of heterochromatin and lay a foundation for further mechanistic dissection of cellular activities that counteract epigenetic gene silencing.

Original languageEnglish
Article numbere1009645
JournalPLOS Genetics
Issue number6
Publication statusPublished - 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright: © 2021 Shimada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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