title: Post-transcriptional control of executioner caspases by RNA-binding proteins.
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.
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.|Molecular Life Sciences PhD Program, Swiss Federal Institute of Technology, University of Zurich, 8057 Zurich, Switzerland.
authors: Deni
authors: D
authors: Subasic
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.|Systems Biology PhD Program, Swiss Federal Institute of Technology, University of Zurich, 8057 Zurich, Switzerland.
authors: Thomas
authors: T
authors: Stoeger
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Seline
authors: S
authors: Eisenring
authors: Faculty of Health and Medical Sciences, Department of Microbial and Cellular Sciences, University of Surrey, Stag Hill Campus, GU2 7XH Guildford, United Kingdom.
authors: Ana M
authors: AM
authors: Matia-González
authors: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
authors: Jochen
authors: J
authors: Imig
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Xue
authors: X
authors: Zheng
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Lei
authors: L
authors: Xiong
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Pascal
authors: P
authors: Gisler
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Ralf
authors: R
authors: Eberhard
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: René
authors: R
authors: Holtackers
authors: Faculty of Health and Medical Sciences, Department of Microbial and Cellular Sciences, University of Surrey, Stag Hill Campus, GU2 7XH Guildford, United Kingdom.
authors: André P
authors: AP
authors: Gerber
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Lucas
authors: L
authors: Pelkmans
authors: Institute of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland.
authors: Michael O
authors: MO
authors: Hengartner
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D012323:RNA Processing, Post-Transcriptional; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D016601:RNA-Binding Proteins; D020169:Caspases
keywords: CED-3; GLD-1; RNA-binding proteins; apoptosis; caspase; caspase-3; translational control