Enhancer of Rudimentary Cooperates with Conserved RNA-Processing Factors to Promote Meiotic mRNA Decay and Facultative Heterochromatin Assembly

Abstract

SUMMARY Erh1, the fission yeast homolog of Enhancer of rudimentary, is implicated in meiotic mRNA elimination during vegetative growth, but its function is poorly understood. We show that Erh1 and the RNA-binding protein Mmi1 form a stoichiometric complex called EMC (Erh1-Mmi1 complex), to promote meiotic mRNA decay and facultative heterochromatin assembly. To perform these functions, EMC associates with two distinct complexes, MTREC (Mtl1-Red1 core) and CCR4-NOT. Whereas MTREC facilitates assembly of heterochromatin islands coating meiotic genes silenced by the nuclear exosome, CCR4-NOT promotes RNAi-dependent heterochromatin domain (HOOD) formation at EMC-target loci. CCR4-NOT also assembles HOODs at retrotransposons and regulated genes containing cryptic introns. We find that CCR4-NOT facilitates HOOD assembly through its association with the conserved Pir2/ARS2 protein, and also maintains rDNA integrity and silencing by promoting heterochromatin formation. Our results reveal connections among Erh1, CCR4-NOT, Pir2/ARS2 and RNAi, which target heterochromatin to regulate gene expression and to protect genome integrity.

Untimely expression of gametogenic genes in vegetative cells causes uniparental disomy

“…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.…”

The Diverse Requirements of ARS2 in nuclear cap-binding complex-dependent RNA Processing

“…Interestingly, published mass spectrometry data show ARS2 can be phosphorylated at Y172 [81] and Y175 [82] within the DUF3546 domain, suggesting the function of this domain may be regulated post-translationally by phosphorylation. In fission yeast, mutation of F165 in the DUF3546 domain contributes to a temperature sensitive allele [83] . How the DUF3546 domain regulates interactions with RNA requires further investigation.…”

“…In S. pombe, Pir2/Ars2 is required for heterochromatin formation at centromeres, telomeres, heterochromatin domains (HOODs), and a subset of meiotic loci [83,90] . Pir2/Ars2 KD results in decreased histone H3 lysine 9 methylation (H3K9me) levels at these sites, a hallmark of heterochromatin formation [83,90] . The requirement of Pir2/Ars2 for heterochromatin formation at these diverse regions involves several partially overlapping pathways.…”

“…The requirement of Pir2/Ars2 for heterochromatin formation at these diverse regions involves several partially overlapping pathways. The best characterized pathway is centromeric silencing, which is mediated by RNA interference (RNAi) machinery and heterochromatin formation [133] , and requires Pir2/Ars2 [83,90] . Transcription from repeat elements in these regions forms dsRNAs, which are cleaved by Dicer to generate siRNAs that are loaded onto an Ago1-containing RNA-induced transcriptional silencing (RITS) complex [134] .…”

“…This complex, along with Pir2/Ars2, mediates heterochromatin formation at telomeres, HOODs, and a subset of meiotic loci [83] . Ccr4-Not in S. pombe is comprised of Ccr4, Caf1, Caf40, and five Not proteins (Not1-5) [138] .…”