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MINA-1 and WAGO-4 are part of regulatory network coordinating germ cell death and RNAi in C. elegans

Sendoel, Ataman, Subasic, Deni, Ducoli, Luca, Keller, Martin, Michel, Erich, Kohler, Ines, Singh, Kapil Dev, Zheng, Xue, Brümmer, Anneke, Imig, Jochen , Kishore, Shivendra, Wu, Yibo, Kanitz, Alexander, Kaech, Andres, Mittal, Nitish, Matia-González, Ana M, Gerber, Andre, Zavolan, Mihaela, Aebersold, Ruedi, Hall, Jonathan, Allain, Frédéric H-T and Hengartner, Michael O (2019) MINA-1 and WAGO-4 are part of regulatory network coordinating germ cell death and RNAi in C. elegans Cell Death and Differentiation, 26. pp. 2157-2178.

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Abstract

Post-transcriptional control of mRNAs by RNA-binding proteins (RBPs) has a prominent role in the regulation of gene expression. RBPs interact with mRNAs to control their biogenesis, splicing, transport, localization, translation, and stability. Defects in such regulation can lead to a wide range of human diseases from neurological disorders to cancer. Many RBPs are conserved between Caenorhabditis elegans and humans, and several are known to regulate apoptosis in the adult C. elegans germ line. How these RBPs control apoptosis is, however, largely unknown. Here, we identify mina-1(C41G7.3) in a RNA interference-based screen as a novel regulator of apoptosis, which is exclusively expressed in the adult germ line. The absence of MINA-1 causes a dramatic increase in germ cell apoptosis, a reduction in brood size, and an impaired P granules organization and structure. In vivo crosslinking immunoprecipitation experiments revealed that MINA-1 binds a set of mRNAs coding for RBPs associated with germ cell development. Additionally, a system-wide analysis of a mina-1 deletion mutant compared to wild type, including quantitative proteome and transcriptome data, hints to a post-transcriptional regulatory RBP network driven by MINA-1 during germ cell development in C. elegans. In particular, we found that the germline-specific Argonaute WAGO-4 protein levels are increased in mina-1 mutant background. Phenotypic analysis of double mutant mina-1;wago-4 revealed that contemporary loss of MINA-1 and WAGO-4 strongly rescues the phenotypes observed in mina-1 mutant background. To strengthen this functional interaction, we found that upregulation of WAGO-4 in mina-1 mutant animals causes hypersensitivity to exogenous RNAi. Our comprehensive experimental approach allowed us to describe a phenocritical interaction between two RBPs controlling germ cell apoptosis and exogenous RNAi. These findings broaden our understanding of how RBPs can orchestrate different cellular events such as differentiation and death in C. elegans.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Sendoel, Ataman
Subasic, Deni
Ducoli, Luca
Keller, Martin
Michel, Erich
Kohler, Ines
Singh, Kapil Dev
Zheng, Xue
Brümmer, Anneke
Imig, Jochen
Kishore, Shivendra
Wu, Yibo
Kanitz, Alexander
Kaech, Andres
Mittal, Nitish
Matia-González, Ana Ma.matia@surrey.ac.uk
Gerber, Andrea.gerber@surrey.ac.uk
Zavolan, Mihaela
Aebersold, Ruedi
Hall, Jonathan
Allain, Frédéric H-T
Hengartner, Michael O
Date : 6 February 2019
Funders : European Union’s Seventh Framework Programme FP7
DOI : 10.1038/s41418-019-0291-z
Grant Title : The People Programme (Marie Curie Actions) - REA grant
Copyright Disclaimer : © 2019 Springer Nature Publishing AG
Depositing User : Melanie Hughes
Date Deposited : 27 Nov 2018 11:54
Last Modified : 28 Oct 2019 14:30
URI: http://epubs.surrey.ac.uk/id/eprint/849939

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