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The C. elegans PUM1, 2-like RNA binding protein PUF-8 is required for robustness of the cell death fate

Xu, Jimei; Jiang, Yanwen; Sherrard, Ryan; Ikegami, Kyoko; Conradt, Barbara; (2023) The C. elegans PUM1, 2-like RNA binding protein PUF-8 is required for robustness of the cell death fate. Development , 150 (19) , Article dev201167. 10.1242/dev.201167. Green open access

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Abstract

During C. elegans development, 1090 somatic cells are generated of which 959 survive and 131 die, many through apoptosis. We present evidence that PUF-8, a C. elegans ortholog of the mammalian RNA binding proteins PUM1 and PUM2, is required for the robustness of this 'survival and death' pattern. We found that PUF-8 prevents the inappropriate death of cells that normally survive, and we present evidence that this anti-apoptotic activity of PUF-8 is dependent on PUF-8's ability to interact with ced-3caspase mRNA thereby repressing the activity of the pro-apoptotic ced-3caspase gene. PUF-8 also promotes the death of cells that are programmed to die, and we propose that this pro-apoptotic activity of PUF-8 may depend on PUF-8's ability to repress the expression of the anti-apoptotic ced-9Bcl-2 gene. Our results suggest that stochastic differences in the expression of genes within the apoptosis pathway can disrupt the highly reproducible and robust survival and death pattern during C. elegans development, and that PUF-8PUM1, 2 acts at the post-transcriptional level to level out these differences, thereby ensuring proper cell number homeostasis.

Type: Article
Title: The C. elegans PUM1, 2-like RNA binding protein PUF-8 is required for robustness of the cell death fate
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.201167
Publisher version: https://doi.org/10.1242/dev.201167
Language: English
Additional information: © 2023. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: C. elegans, apoptosis, ced-3 caspase, ced-9 Bcl-2, cell number homeostasis, developmental robustness
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10177864
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