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A Genetic Program Mediates Cold-warming Response and Promotes Stress-induced Phenoptosis in C. elegans

By Wei Jiang, Yuehua Wei, Yong Long, Arthur Owen, Bingying Wang, Xuebing Wu, Shuo Luo, Yongjun Dang, Dengke K. Ma

Posted 24 Feb 2018
bioRxiv DOI: 10.1101/271106 (published DOI: 10.7554/eLife.35037)

How multicellular organisms respond to and are impacted by severe hypothermic stress is largely unknown. From C. elegans screens for mutants abnormally responding to cold-warming stimuli, we identify a molecular genetic pathway comprising ISY-1, a conserved uncharacterized protein, and ZIP-10, a bZIP-type transcription factor. ISY-1 gatekeeps the ZIP-10 transcriptional program by regulating the microRNA mir-60. Downstream of ISY-1 and mir-60, zip-10 levels rapidly and specifically increase upon transient cold-warming response. Prolonged zip-10 up-regulation induces several protease-encoding genes and promotes stress-induced organismic death, or phenoptosis, of C. elegans. zip-10 deficiency confers enhanced resistance to prolonged cold-warming stress, more prominently in adults than larvae. We conclude that the ZIP-10 genetic program mediates cold-warming response and may have evolved to promote wild-population kin selection under resource-limiting and thermal stress conditions.

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