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

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 game...

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Autores principales: Xie, Guodong, Vo, Tommy V., Thillainadesan, Gobi, Holla, Sahana, Zhang, Beibei, Jiang, Yiyang, Lv, Mengqi, Xu, Zheng, Wang, Chongyuan, Balachandran, Vanivilasini, Shi, Yunyu, Li, Fudong, Grewal, Shiv I. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335422/
https://www.ncbi.nlm.nih.gov/pubmed/30651569
http://dx.doi.org/10.1038/s41467-018-08273-9
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author Xie, Guodong
Vo, Tommy V.
Thillainadesan, Gobi
Holla, Sahana
Zhang, Beibei
Jiang, Yiyang
Lv, Mengqi
Xu, Zheng
Wang, Chongyuan
Balachandran, Vanivilasini
Shi, Yunyu
Li, Fudong
Grewal, Shiv I. S.
author_facet Xie, Guodong
Vo, Tommy V.
Thillainadesan, Gobi
Holla, Sahana
Zhang, Beibei
Jiang, Yiyang
Lv, Mengqi
Xu, Zheng
Wang, Chongyuan
Balachandran, Vanivilasini
Shi, Yunyu
Li, Fudong
Grewal, Shiv I. S.
author_sort Xie, Guodong
collection PubMed
description 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 Mmi1(Trp112) 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 mmi1(W112A). Our study delineates EMC requirements in gene silencing and identifies an ERH interface required for interaction with an RNA binding protein.
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spelling pubmed-63354222019-01-18 A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing Xie, Guodong Vo, Tommy V. Thillainadesan, Gobi Holla, Sahana Zhang, Beibei Jiang, Yiyang Lv, Mengqi Xu, Zheng Wang, Chongyuan Balachandran, Vanivilasini Shi, Yunyu Li, Fudong Grewal, Shiv I. S. Nat Commun Article 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 Mmi1(Trp112) 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 mmi1(W112A). Our study delineates EMC requirements in gene silencing and identifies an ERH interface required for interaction with an RNA binding protein. Nature Publishing Group UK 2019-01-16 /pmc/articles/PMC6335422/ /pubmed/30651569 http://dx.doi.org/10.1038/s41467-018-08273-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Xie, Guodong
Vo, Tommy V.
Thillainadesan, Gobi
Holla, Sahana
Zhang, Beibei
Jiang, Yiyang
Lv, Mengqi
Xu, Zheng
Wang, Chongyuan
Balachandran, Vanivilasini
Shi, Yunyu
Li, Fudong
Grewal, Shiv I. S.
A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
title A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
title_full A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
title_fullStr A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
title_full_unstemmed A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
title_short A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
title_sort conserved dimer interface connects erh and yth family proteins to promote gene silencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335422/
https://www.ncbi.nlm.nih.gov/pubmed/30651569
http://dx.doi.org/10.1038/s41467-018-08273-9
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