Mmi1 RNA surveillance machinery directs RNAi complex RITS to specific meiotic genes in fission yeast

Abstract

RNA interference (RNAi) silences gene expression by acting both at the transcriptional and post-transcriptional levels in a broad range of eukaryotes. In the fission yeast Schizosaccharomyces pombe the RNA-Induced Transcriptional Silencing (RITS) RNAi complex mediates heterochromatin formation at non-coding and repetitive DNA. However, the targeting and role of RITS at other genomic regions, including protein-coding genes, remain unknown. Here we show that RITS localizes to specific meiotic genes and mRNAs. Remarkably, RITS is guided to these meiotic targets by the RNA-binding protein Mmi1 and its associated RNA surveillance machinery that together degrade selective meiotic mRNAs during vegetative growth. Upon sexual differentiation, RITS localization to the meiotic genes and mRNAs is lost. Large-scale identification of Mmi1 RNA targets reveals that RITS subunit Chp1 associates with the vast majority of them. In addition, loss of RNAi affects the effective repression of sexual differentiation mediated by the Mmi1 RNA surveillance machinery. These findings uncover a new mechanism for recruiting RNAi to specific meiotic genes and suggest that RNAi participates in the control of sexual differentiation in fission yeast.

Conserved factor Dhp1/Rat1/Xrn2 triggers premature transcription termination and nucleates heterochromatin to promote gene silencing

“…In addition to their role in transcriptional control, RNA surveillance factors closely monitor the transcriptome. In S. pombe, RNA elimination factors selectively degrade meiotic mRNAs in vegetative cells (11,(14)(15)(16)40). In this study, we uncover a mode of gene silencing that requires close cooperation between RNA degradation and transcription termination factors.…”

“…S1A). Because RNA elimination factors promote the assembly of facultative heterochromatin on meiotic genes (13)(14)(15), premature termination could be mediated through heterochromatin formation. Strikingly, we found that the loss of Clr4, the sole H3K9 methyltransferase in S. pombe that is essential for formation of heterochromatin islands (15), did not affect premature transcription termination (Fig.…”

“…RNA-processing factors such as MTREC also promote RNAiindependent assembly of facultative heterochromatin islands, which are modified in response to nutritional signals such as nitrogen starvation (11,(13)(14)(15). Heterochromatin islands preferentially target meiotic genes that are silenced during vegetative growth (15).…”

Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy

“…Independently of heterochromatin assembly, RNAi silences meiotic genes during vegetative growth 10,11 . The untimely expression of gametogenic genes, which has been found to occur in tumors in humans 12,13 and to induce tumorigenesis in Drosophila 14 , might be linked to aneuploidy observed in cancer cells.…”

“…The YTH-family protein Mmi1 promotes degradation of meiotic gene transcripts by RNAi and the nuclear exosome 10,11,15–18 . Comparing the expression profiles of cells lacking RNAi components or Mmi1 revealed that a majority of the meiotic genes that were upregulated in ago1 ∆ or dcr1 ∆ RNAi mutants (85 out of 152) were also upregulated in mmi1 ∆ (Fig.…”