PreprintCited by 44Genetics, Aging, and Longevity in Model OrganismsRNA Research and SplicingRNA and protein synthesis mechanisms

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Dietary restriction induces post-transcriptional regulation of longevity genes

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Preprint — published as 10.26508/lsa.201800281

Abstract

Dietary restriction increases lifespan through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of C. elegans subjected to dietary restriction. Transcription of muscle regulatory and structural genes increased, while increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of post-transcriptional regulation identified putative roles for RNA binding proteins, RNA editing, microRNA, alternative splicing, and nonsense mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate lifespan. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally downregulated genes. Furthermore, 3’ UTR editing and intron retention increase under dietary restriction and correlate with diminished translation, while trans-spliced genes are refractory to reduced translation efficiency compared to messages with the native 5’ UTR. Finally, we find that smg-6 and smg-7 , which are genes governing selection and turnover of nonsense mediated decay targets, are required for increased lifespan under dietary restriction.

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Metadata

Authors
Rollins, J. A., Snow, S. S., Kapahi, P., & Rogers, A. N.
Affiliations
  • Mount Desert Island Biological Laboratory (US)
  • Buck Institute for Research on Aging (US)
Corresponding author
  • Rollins, Jarod A.
  • Rogers, Aric N.
Venue
Life Science Alliance
Publisher
openRxiv
Published
2019-02-28
Volume
2
Issue
4
Pages
e201800281-e201800281
ISSN
2575-1077 (ISSN-L)
OpenAlex
W2955977336
Cited by
44
References
1
Citations by year
2026: 5 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 5 · 2020: 5 · 2019: 3
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Life Science Alliance (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ellison Medical Foundation (AG-NS-1087-13)
  • National Institutes of Health (P20 GM0103423, OD010440, P40OD010440)
  • National Institute on Aging (R21AG056743, R00AG037621)
  • National Institute of General Medical Sciences (P20GM104318, P20GM0103423, P20GM103423)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
dietary restriction, longevity, Caenorhabditis elegans, post-transcriptional regulation, translational regulation, transcriptome, translatome, RNA editing, intron retention, trans-splicing, nonsense-mediated mRNA decay, microRNA, alternative splicing, neuropeptide signaling, amino acid metabolism, nutrient limitation, lifespan
MeSH terms
RNA-Binding Motifs, Amino Acids, Animals, Carrier Proteins, Endoribonucleases, Gene Expression Regulation, Introns, Longevity, Muscle Proteins, Neuropeptides, RNA, Messenger, Protein Biosynthesis, Caenorhabditis elegans, Alternative Splicing, Telomerase, 5' Untranslated Regions, 3' Untranslated Regions, Caloric Restriction, RNA Interference, MicroRNAs, Transcriptome

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