RNAi-Mediated Targeting of Heterochromatin by the RITS Complex

TLDR

RNA interference is a widespread silencing mechanism acting at both posttranscriptional and transcriptional levels. The study purifies the RNAi effector complex RITS, required for heterochromatin assembly in fission yeast. RITS comprises Ago1, Chp1, Tas3, and Dicer‑dependent small RNAs that guide the complex to heterochromatic regions. These centromere‑repeat‑derived small RNAs are essential for RITS localization, revealing how RNAi directs heterochromatin formation and epigenetic silencing at specific loci.

Abstract

RNA interference (RNAi) is a widespread silencing mechanism that acts at both the posttranscriptional and transcriptional levels. Here, we describe the purification of an RNAi effector complex termed RITS (RNA-induced initiation of transcriptional gene silencing) that is required for heterochromatin assembly in fission yeast. The RITS complex contains Ago1 (the fission yeast Argonaute homolog), Chp1 (a heterochromatin-associated chromodomain protein), and Tas3 (a novel protein). In addition, the complex contains small RNAs that require the Dicer ribonuclease for their production. These small RNAs are homologous to centromeric repeats and are required for the localization of RITS to heterochromatic domains. The results suggest a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci.