Regulation of Heterochromatic Silencing and Histone H3 Lysine-9 Methylation by RNAi

TLDR

Eukaryotic heterochromatin, rich in repeats and transposons and marked by modified histones, regulates gene expression and chromosome segregation. The study proposes that centromeric repeat‑derived double‑stranded RNA directs heterochromatin formation and maintenance via RNAi. The authors deleted argonaute, dicer, and RNA‑dependent RNA polymerase genes in Schizosaccharomyces pombe to disrupt RNAi and assess its role in heterochromatin. Loss of RNAi components caused accumulation of centromeric transcripts, derepression of centromere‑integrated transgenes, loss of H3K9 methylation, and impaired centromere function.

Abstract

Eukaryotic heterochromatin is characterized by a high density of repeats and transposons, as well as by modified histones, and influences both gene expression and chromosome segregation. In the fission yeast Schizosaccharomyces pombe , we deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference (RNAi). Deletion results in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats. This is accompanied by transcriptional de-repression of transgenes integrated at the centromere, loss of histone H3 lysine-9 methylation, and impairment of centromere function. We propose that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi.