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RNA helicase HEL-1 promotes longevity by specifically activating DAF-1…

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DOI: http://dx.doi.org/10.1073/pnas.1505451112

Mihwa Seoa, Keunhee Seo, Wooseon Hwang, Hee Jung Koo, Jeong-Hoon Hahm, Jae-Seong Yang, Seong Kyu Han, Daehee Hwang, Sanguk Kim, Sung Key Jang, Yoontae Lee, Hong Gil Nam, and Seung-Jae V. Lee


Published: 03 Aug 2015.


The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans.


Keywords: C. elegans; aging; FOXO; insulin/IGF-1; RNA helicase;


Link: http://www.pnas.org/content/112/31/E4246.abstract


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