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Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4246-55. doi: 10.1073/pnas.1505451112. Epub 2015 Jul 20.

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

Author information

1
Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea;
2
Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
3
Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea;
4
School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea;
5
Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea;
6
School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea;
7
Center for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea; nam@dgist.ac.kr seungjaelee@postech.ac.kr.
8
School of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea; Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea; Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang 790-784, Korea nam@dgist.ac.kr seungjaelee@postech.ac.kr.

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; FOXO; RNA helicase; aging; insulin/IGF-1

PMID:
26195740
PMCID:
PMC4534234
DOI:
10.1073/pnas.1505451112
[Indexed for MEDLINE]
Free PMC Article

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