Pharmaceutical Sciences Faculty Publications

Title

Clr4/Suv39 and RNA Quality Control Factors Cooperate to Trigger RNAi and Suppress Antisense RNA

Document Type

Article

Publication Date

3-25-2011

Journal Title

Science

ISSN

1095-9203

Volume

331

Issue

6024

First Page

1624

Last Page

1627

DOI

10.1126/science.1198712

PubMed ID

21436456

PubMed Central® ID

PMC6309853

Abstract

Pervasive transcription of eukaryotic genomes generates a plethora of noncoding RNAs. In fission yeast, the heterochromatin factor Clr4/Suv39 methyltransferase facilitates RNA interference (RNAi)-mediated processing of centromeric transcripts into small interfering RNAs (siRNAs). Clr4 also mediates degradation of antisense RNAs at euchromatic loci, but the underlying mechanism has remained elusive. We show that Clr4 and the RNAi effector RITS (RNA-induced transcriptional silencing) interact with Mlo3, a protein related to mRNA quality control and export factors. Loss of Clr4 impairs RITS interaction with Mlo3, which is required for centromeric siRNA production and antisense suppression. Mlo3 also interacts with the RNA surveillance factor TRAMP, which suppresses antisense RNAs targeted by Clr4 and RNAi. These findings link Clr4 to RNA quality control machinery and suggest a pathway for processing potentially deleterious RNAs through the coordinated actions of RNAi and other RNA processing activities.

Keywords

Cell cycle proteins, centromere, histones, mutation, RNA interference, RNA processing, RNA, antisense

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