6s2w
Structure of S. pombe Erh1, a protein important for meiotic mRNA decay in mitosis and meiosis progression.
Structural highlights
FunctionERH_SCHPO Forms part of the erh1-mmi1 complex that recruits the CCR4-NOT complex and the NURS complex to target RNAs (PubMed:26942678, PubMed:30651569, PubMed:31974447). Suppresses the meiotic program during vegetative growth and promotes the meiotic program during mating (PubMed:31974447). Recruitment of the NURS complex to target mRNAs promotes mRNA decay by engagement of the nuclear exosome, and formation of heterochromatin islands at meiotic genes silenced by the exosome (PubMed:26942678). Recruitment of the CCR4-NOT complex to target RNAs promotes heterochromatin formation at RNAi-dependent heterochromatin domains (HOODs), including a subset of meiotic genes, lncRNAs and retrotransposons (PubMed:26942678). Recruitment of the CCR4-NOT complex to rDNA promotes rDNA heterochromatin assembly (PubMed:26942678).[1] [2] [3] Publication Abstract from PubMedTimely and accurate expression of the genetic information relies on the integration of environmental cues and the activation of regulatory networks involving transcriptional and post-transcriptional mechanisms. In fission yeast, meiosis-specific transcripts are selectively targeted for degradation during mitosis by the EMC complex, composed of Erh1, the ortholog of human ERH, and the YTH family RNA-binding protein Mmi1. Here, we present the crystal structure of Erh1 and show that it assembles as a homodimer. Mutations of amino acid residues to disrupt Erh1 homodimer formation result in loss-of-function phenotypes, similar to erh1 cells: expression of meiotic genes is derepressed in mitotic cells and meiosis progression is severely compromised. Interestingly, formation of Erh1 homodimer is dispensable for interaction with Mmi1, suggesting that only fully assembled EMC complexes consisting of two Mmi1 molecules bridged by an Erh1 dimer are functionally competent. We also show that Erh1 does not contribute to Mmi1-dependent down-regulation of the meiosis regulator Mei2, supporting the notion that Mmi1 performs additional functions beyond EMC. Overall, our results provide a structural basis for the assembly of the EMC complex and highlight its biological relevance in gametogenic gene silencing and meiosis progression. Formation of S. pombe Erh1 homodimer mediates gametogenic gene silencing and meiosis progression.,Hazra D, Andric V, Palancade B, Rougemaille M, Graille M Sci Rep. 2020 Jan 23;10(1):1034. doi: 10.1038/s41598-020-57872-4. PMID:31974447[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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