Mihwa Seoa,b, Keunhee Seoc, Wooseon Hwangc, Hee Jung Kooa,b, Jeong-Hoon Hahma, Jae-Seong Yangb,1, Seong Kyu Hanc, Daehee Hwanga,d, Sanguk Kimb,c,e, Sung Key Jangc, Yoontae Leec, Hong Gil Nama,d,2, and Seung-Jae V. Leeb,c,e,2
aCenter for Plant Aging Research, Institute for Basic Science, Daegu 711-873, Korea;
bSchool of Interdisciplinary Bioscience and Bioengineering Pohang University of Science and Technology, Pohang 790-784, Korea;
cDepartment of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea;
dDepartment of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea;
eInformation Technology Convergence Engineering, Pohang University of Science and Technology, Pohang 790-784, Korea
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.
C. elegans, aging, FOXO, insulin/IGF-1, RNA helicase
1Present address: European Molecular Biology Laboratory/Centre for Genomic Regulation Systems Biology Research Unit, Centre for Genomic Regulation, 08003 Barcelona, Spain.
2To whom correspondence may be addressed.
Author contributions: M.S., H.G.N., and S.-J.V.L. designed research; M.S., K.S., W.H., H.J.K., J.-H.H., J.-S.Y., S.K.H., Y.L., and S.-J.V.L. performed research; S.K., S.K.J., and Y.L. contributed new reagents/analytic tools; M.S., H.J.K., J.-S.Y., S.K.H., and D.H. analyzed data; and M.S., H.G.N., and S.-J.V.L. wrote the paper.