edoc

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

Sendoel, Ataman and Subasic, Deni and Ducoli, Luca and Keller, Martin and Michel, Erich and Kohler, Ines and Singh, Kapil Dev and Zheng, Xue and Brümmer, Anneke and Imig, Jochen and Kishore, Shivendra and Wu, Yibo and Kanitz, Alexander and Kaech, Andres and Mittal, Nitish and Matia-González, Ana M. and Gerber, André P. and Zavolan, Mihaela and Aebersold, Ruedi and Hall, Jonathan and 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 & Differentiation subscription, 26 (10). pp. 2157-2178.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/69468/

Downloads: Statistics Overview

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 with 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela and Brümmer, Anneke and Imig, Jochen and Kishore, Shivendra and Kanitz, Alexander and Mittal, Nitish
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:1350-9047
e-ISSN:1476-5403
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 Aug 2020 15:05
Deposited On:13 Aug 2020 15:05

Repository Staff Only: item control page