title: Clr4/Suv39 and RNA quality control factors cooperate to trigger RNAi and suppress antisense RNA.
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.
authors: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute/NIH, Bethesda, MD 20892, USA.
authors: Ke
authors: K
authors: Zhang
authors: Tamas
authors: T
authors: Fischer
authors: Rebecca L
authors: RL
authors: Porter
authors: Jothy
authors: J
authors: Dhakshnamoorthy
authors: Martin
authors: M
authors: Zofall
authors: Ming
authors: M
authors: Zhou
authors: Timothy
authors: T
authors: Veenstra
authors: Shiv I S
authors: SI
authors: Grewal
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism; D022041:Euchromatin / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D016372:RNA, Antisense / Q000378:metabolism*; D012331:RNA, Fungal / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C115018:Chp1 protein, S pombe; D022041:Euchromatin; D006657:Histones; C503583:Mlo3 protein, S pombe; D016372:RNA, Antisense; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C112744:clr4 protein, S pombe