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.

doi:10.1038/s41467-018-08273-9

Cited by 37 publications

(87 citation statements)

References 64 publications

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“…S2), indicating that Erh1 does not contribute to Mei2 down-regulation in mitotic cells. This is also consistent with the notion that Mmi1 can exert functions independently of Erh1, as in case of transcription termination 20,30 .…”

Section: Formation Of Erh1 Homodimer Is Required For Gametogenic Genesupporting

confidence: 91%

“…An evolutionary highly conserved region present on the side of the homodimerization surface has been shown to participate in the interaction with Mmi1 (a short region encompassing residues 95-122; 20 ) while this work was in progress ( Fig. 1E).…”

Section: An Evolutionary Conserved Homodimermentioning

confidence: 99%

“…Recent works showed that Erh1 and Mmi1 form a 2:2 stoichiometric complex dubbed EMC (for Erh1-Mmi1 complex) whereby two Mmi1 peptides are physically bridged by an Erh1 homodimer 17,19,20 . EMC localizes to scattered nuclear foci in vegetative cells and associates with two distinct complexes 19,21 .…”

Section: !mentioning

confidence: 99%

“…Here, we describe the crystal structure of S. pombe Erh1 protein and compare it to the structures of metazoan ERH proteins that have already been solved as well as to the structure of the S. pombe Erh1-Mmi1 complex that has been solved while this work was in progress 20 . We observe that Erh1 organizes as a homodimer in which the two monomers contact each other via !…”

Section: !mentioning

confidence: 99%

“…In vegetative cells, Erh1 and Mmi1 assemble in the EMC complex that localizes to nuclear foci 17,19,20 . Live cell microscopy experiments revealed lower and diffuse GFP-Erh1I11R,L13R signals when compared to GFP-Erh1 ( Fig.…”

Section: Formation Of Erh1 Homodimer Is Required For Gametogenic Genementioning

confidence: 99%

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Formation ofS. pombeErh1 homodimer mediates gametogenic gene silencing and meiosis progression

Hazra¹,

Andric²,

Palancade³

et al. 2019

Preprint

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Timely and accurate expression of the genetic information relies on the integration of environmental cues and the activation of regulatory networks involving transcriptional and posttranscriptional 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.! 1

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Section: Formation Of Erh1 Homodimer Is Required For Gametogenic Genesupporting

confidence: 91%

Section: An Evolutionary Conserved Homodimermentioning

confidence: 99%

Section: !mentioning

confidence: 99%

Section: !mentioning

confidence: 99%

Section: Formation Of Erh1 Homodimer Is Required For Gametogenic Genementioning

confidence: 99%

See 3 more Smart Citations

Formation ofS. pombeErh1 homodimer mediates gametogenic gene silencing and meiosis progression

Hazra¹,

Andric²,

Palancade³

et al. 2019

Preprint

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ERH proteins: connecting RNA processing to tumorigenesis?

Graille

2020

Curr Genet

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With the development of-omics approaches, the scientific community is now submerged by a wealth of information that can be used to analyze various parameters: the degree of protein sequence conservation, protein 3D structures as well as RNA and protein expression levels in various benign and tumor tissues, during organism development or upon exposure to chemicals such as endocrine disrupters. However, if such information can be used to identify genes with potentially important biological function, additional studies are needed to deeply characterize their cellular function in model organisms. Here, we discuss the case of such a gene: ERH, encoding a highly conserved homodimeric protein found in unicellular eukaryotes, plants and metazoan, of yet unknown biological function, which might be linked to mRNA metabolism and that is emerging as important for cell migration and metastasis.

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Comprehensive gene expression analysis after ERH gene knockdown in human bladder cancer T24 cell lines

Pang

Hao

Chen

et al. 2020

Gene

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

Cited by 37 publications

References 64 publications

Formation ofS. pombeErh1 homodimer mediates gametogenic gene silencing and meiosis progression

Formation ofS. pombeErh1 homodimer mediates gametogenic gene silencing and meiosis progression

ERH proteins: connecting RNA processing to tumorigenesis?

Comprehensive gene expression analysis after ERH gene knockdown in human bladder cancer T24 cell lines

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