An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila.
Drosophila
ageing
alternative splicing
backsplicing
circRNA
heparan sulfate
insulin
longevity
non-coding RNAs
sulfateless
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
16 07 2020
16 07 2020
Historique:
received:
03
05
2019
revised:
21
04
2020
accepted:
04
06
2020
pubmed:
28
6
2020
medline:
1
9
2020
entrez:
28
6
2020
Statut:
ppublish
Résumé
Circular RNAs (circRNAs) are abundant and accumulate with age in neurons of diverse species. However, only few circRNAs have been functionally characterized, and their role during aging has not been addressed. Here, we use transcriptome profiling during aging and find that accumulation of circRNAs is slowed down in long-lived insulin mutant flies. Next, we characterize the in vivo function of a circRNA generated by the sulfateless gene (circSfl), which is consistently upregulated, particularly in the brain and muscle, of diverse long-lived insulin mutants. Strikingly, lifespan extension of insulin mutants is dependent on circSfl, and overexpression of circSfl alone is sufficient to extend the lifespan. Moreover, circSfl is translated into a protein that shares the N terminus and potentially some functions with the full-length Sfl protein encoded by the host gene. Our study demonstrates that insulin signaling affects global circRNA accumulation and reveals an important role of circSfl during aging in vivo.
Identifiants
pubmed: 32592682
pii: S1097-2765(20)30396-8
doi: 10.1016/j.molcel.2020.06.011
pmc: PMC7318944
pii:
doi:
Substances chimiques
Drosophila Proteins
0
Insulin
0
RNA, Circular
0
Sulfotransferases
EC 2.8.2.-
sfl protein, Drosophila
EC 2.8.2.8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
268-279.e5Subventions
Organisme : NIH HHS
ID : P40 OD018537
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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