Τίτλος:
MRNA decapping is an evolutionarily conserved modulator of neuroendocrine signaling that controls development and ageing
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Eukaryotic 5’ 3’ mRNA decay plays important roles during development and in response to stress, regulating gene expression post-transcriptionally. In Caenorhabditis elegans, deficiency of DCAP-1/DCP1, the essential co-factor of the major cytoplasmic mRNA decapping enzyme, impacts normal development, stress survival and ageing. Here, we show that overexpression of dcap-1 in neurons of worms is sufficient to increase lifespan through the function of the insulin/IGF-like signaling and its effector DAF-16/FOXO transcription factor. Neuronal DCAP-1 affects basal levels of INS-7, an ageing-related insulin-like peptide, which acts in the intestine to determine lifespan. Short-lived dcap-1 mutants exhibit a neurosecretion-dependent upregulation of intestinal ins-7 transcription, and diminished nuclear localization of DAF-16/FOXO. Moreover, neuronal overexpression of DCP1 in Drosophila melanogaster confers longevity in adults, while neuronal DCP1 deficiency shortens lifespan and affects wing morphogenesis, cell non-autonomously. Our genetic analysis in two model-organisms suggests a critical and conserved function of DCAP-1/DCP1 in developmental events and lifespan modulation. © 2020, eLife Sciences Publications Ltd. All rights reserved.
Συγγραφείς:
Borbolis, F.
Rallis, J.
Kanatouris, G.
Kokla, N.
Karamalegkos, A.
Vasileiou, C.
Vakaloglou, K.M.
Diallinas, G.
Stravopodis, D.J.
Zervas, C.G.
Syntichaki, P.
Εκδότης:
eLife Sciences Publications Ltd
Λέξεις-κλειδιά:
genomic DNA; messenger RNA; neuropeptide; relaxin 3; transcription factor; transcription factor FOXO; Caenorhabditis elegans protein; daf-16 protein, C elegans; DCAP-1 protein, C elegans; Drosophila protein; forkhead transcription factor; FOXO protein, Drosophila; messenger RNA; ribonuclease, aging; Article; bacterial strain; bacterium culture; comparative study; Drosophila melanogaster; epidermis; evolutionary adaptation; gene construct; gene overexpression; genetic analysis; lifespan; microscopy; nerve cell differentiation; neurosecretory terminal; nuclear localization signal; real time reverse transcription polymerase chain reaction; RNA isolation; RNAi therapeutics; stress; aging; animal; Caenorhabditis elegans; gene expression regulation; genetics; growth, development and aging; nerve cell; neuroendocrine system; physiology; RNA stability, Aging; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Drosophila melanogaster; Drosophila Proteins; Endoribonucleases; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Neurons; Neurosecretory Systems; RNA Stability; RNA, Messenger
