RRC ID 59435
Author Amrit FRG, Naim N, Ratnappan R, Loose J, Mason C, Steenberge L, McClendon BT, Wang G, Driscoll M, Yanowitz JL, Ghazi A.
Title The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity.
Journal Nat Commun
Abstract Stress resistance and longevity are positively correlated but emerging evidence indicates that they are physiologically distinct. Identifying factors with distinctive roles in these processes is challenging because pro-longevity genes often enhance stress resistance. We demonstrate that TCER-1, the Caenorhabditis elegans homolog of human transcription elongation and splicing factor, TCERG1, has opposite effects on lifespan and stress resistance. We previously showed that tcer-1 promotes longevity in germline-less C. elegans and reproductive fitness in wild-type animals. Surprisingly, tcer-1 mutants exhibit exceptional resistance against multiple stressors, including infection by human opportunistic pathogens, whereas, TCER-1 overexpression confers immuno-susceptibility. TCER-1 inhibits immunity only during fertile stages of life. Elevating its levels ameliorates the fertility loss caused by infection, suggesting that TCER-1 represses immunity to augment fecundity. TCER-1 acts through repression of PMK-1 as well as PMK-1-independent factors critical for innate immunity. Our data establish key roles for TCER-1 in coordinating immunity, longevity and fertility, and reveal mechanisms that distinguish length of life from functional aspects of aging.
Volume 10(1)
Pages 3042
Published 2019-7-17
DOI 10.1038/s41467-019-10759-z
PII 10.1038/s41467-019-10759-z
PMID 31316054
PMC PMC6637209
MeSH Aging / genetics Aging / immunology Animals Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / immunology Caenorhabditis elegans Proteins / metabolism* Disease Susceptibility / immunology Fertility / genetics Gene Expression Regulation / physiology* Immunity, Innate / genetics* Longevity / genetics* Mitogen-Activated Protein Kinases / genetics Models, Animal Mutation Peptide Elongation Factors / genetics Peptide Elongation Factors / immunology Peptide Elongation Factors / metabolism* Stress, Physiological / genetics Stress, Physiological / immunology*
IF 11.878
Times Cited 3
C.elegans tm1452