A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing

Nat Commun. 2019 Jan 16;10(1):251. doi: 10.1038/s41467-018-08273-9.


Gene regulatory mechanisms rely on a complex network of RNA processing factors to prevent untimely gene expression. In fission yeast, the highly conserved ortholog of human ERH, called Erh1, interacts with the YTH family RNA binding protein Mmi1 to form the Erh1-Mmi1 complex (EMC) implicated in gametogenic gene silencing. However, the structural basis of EMC assembly and its functions are poorly understood. Here, we present the co-crystal structure of the EMC that consists of Erh1 homodimers interacting with Mmi1 in a 2:2 stoichiometry via a conserved molecular interface. Structure-guided mutation of the Mmi1Trp112 residue, which is required for Erh1 binding, causes defects in facultative heterochromatin assembly and gene silencing while leaving Mmi1-mediated transcription termination intact. Indeed, EMC targets masked in mmi1∆ due to termination defects are revealed in mmi1W112A. Our study delineates EMC requirements in gene silencing and identifies an ERH interface required for interaction with an RNA binding protein.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Chromatin Assembly and Disassembly / genetics
  • Gene Expression Regulation, Fungal
  • Gene Silencing*
  • Meiosis / genetics
  • Protein Binding / genetics*
  • Protein Multimerization / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / chemistry
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Transcription Termination, Genetic
  • mRNA Cleavage and Polyadenylation Factors / chemistry
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • Carrier Proteins
  • Erh1 protein, S pombe
  • Mmi1 protein, S pombe
  • RNA, Long Noncoding
  • Schizosaccharomyces pombe Proteins
  • mRNA Cleavage and Polyadenylation Factors