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RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans.

Title
RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans.
Authors
Seo, MSeo, KHwang, WKoo, HJHahm, JHYang, JSHan, SKHwang, DKim, SJang, SKLee, YNam, HGLee, SJV
POSTECH Authors
Kim, SJang, SKLee, YLee, SJV
Date Issued
Aug-2015
Publisher
The NationalAcademy of Sciences
Abstract
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; DATA INTEGRATION METHODOLOGY; C-ELEGANS; LIFE-SPAN; GENE-EXPRESSION; SYSTEMS BIOLOGY; BINDING-PROTEIN; EXPORT FACTOR; ROLES; YEAST; IDENTIFICATION
URI
http://oasis.postech.ac.kr/handle/2014.oak/13465
DOI
10.1073/PNAS.1505451112
ISSN
0027-8424
Article Type
Article
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 112, no. 31, page. E4246 - E4255, 2015-08
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 KIM, SANGUK
Dept of Life Sciences
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