Post-transcriptional control of executioner caspases by RNA-binding proteins

Subasic, D, Stoeger, T, Eisenring, S, Matia-González, AM, Imig, J, Zheng, X, Xiong, L, Gisler, P, Eberhard, R, Holtackers, R et al, Gerber, AP, Pelkmans, L and Hengartner, MO (2016) Post-transcriptional control of executioner caspases by RNA-binding proteins Genes and Development, 30. pp. 2213-2225.

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Abstract

Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)—PUF-8, MEX-3, GLD-1, and CGH-1—that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of executioner caspases by RBPs might be a strategy used widely across the animal kingdom to control apoptosis.

Item Type:	Article
Subjects :	Biosciences and Medicine
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Subasic, D Stoeger, T Eisenring, S Matia-González, AM Imig, J Zheng, X Xiong, L Gisler, P Eberhard, R Holtackers, R Gerber, AP Pelkmans, L Hengartner, MO
Date :	2016
DOI :	10.1101/gad.285726.116
Copyright Disclaimer :	© 2016 Subasic et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/ licenses/by-nc/4.0/.
Uncontrolled Keywords :	CED-3; GLD-1; RNA-binding proteins; apoptosis; caspase; caspase-3; translational control
Depositing User :	Symplectic Elements
Date Deposited :	28 Oct 2016 09:05
Last Modified :	01 Dec 2016 10:54
URI:	http://epubs.surrey.ac.uk/id/eprint/812657

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