Format

Send to

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

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

Author information

1
Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, 230026, Hefei, China.
2
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
3
Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, 230026, Hefei, China. lifudong@ustc.edu.cn.
4
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. grewals@mail.nih.gov.

Abstract

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center