eprintid: 10107572 rev_number: 14 eprint_status: archive userid: 608 dir: disk0/10/10/75/72 datestamp: 2020-08-12 14:31:02 lastmod: 2021-09-19 22:21:18 status_changed: 2020-08-12 14:31:02 type: article metadata_visibility: show creators_name: Weigelt, CM creators_name: Sehgal, R creators_name: Tain, LS creators_name: Cheng, J creators_name: Eßer, J creators_name: Pahl, A creators_name: Dieterich, C creators_name: Grönke, S creators_name: Partridge, L title: An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: F99 note: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: 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. date: 2020-07-16 date_type: published official_url: https://doi.org/10.1016/j.molcel.2020.06.011 oa_status: green full_text_type: pub pmcid: PMC7318944 language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1796657 doi: 10.1016/j.molcel.2020.06.011 pii: S1097-2765(20)30396-8 lyricists_name: Partridge, Linda lyricists_id: LPART24 actors_name: Partridge, Linda actors_name: Wright, Michael actors_id: LPART24 actors_id: MWRIG83 actors_role: owner actors_role: impersonator full_text_status: public publication: Molecular Cell volume: 79 number: 2 pagerange: 268-279.e5 event_location: United States citation: Weigelt, CM; Sehgal, R; Tain, LS; Cheng, J; Eßer, J; Pahl, A; Dieterich, C; ... Partridge, L; + view all <#> Weigelt, CM; Sehgal, R; Tain, LS; Cheng, J; Eßer, J; Pahl, A; Dieterich, C; Grönke, S; Partridge, L; - view fewer <#> (2020) An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila. Molecular Cell , 79 (2) 268-279.e5. 10.1016/j.molcel.2020.06.011 <https://doi.org/10.1016/j.molcel.2020.06.011>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10107572/1/main.pdf