A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging
Open Access
- 25 February 2021
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
A hallmark of aging is loss of differentiated cell identity. Aged Drosophila midgut differentiated enterocytes (ECs) lose their identity, impairing tissue homeostasis. To discover identity regulators, we performed an RNAi screen targeting ubiquitin-related genes in ECs. Seventeen genes were identified, including the deubiquitinase Non-stop (CG4166). Lineage tracing established that acute loss of Non-stop in young ECs phenocopies aged ECs at cellular and tissue levels. Proteomic analysis unveiled that Non-stop maintains identity as part of a Non-stop identity complex (NIC) containing E(y)2, Sgf11, Cp190, (Mod) mdg4, and Nup98. Non-stop ensured chromatin accessibility, maintaining the EC-gene signature, and protected NIC subunit stability. Upon aging, the levels of Non-stop and NIC subunits declined, distorting the unique organization of the EC nucleus. Maintaining youthful levels of Non-stop in wildtype aged ECs safeguards NIC subunits, nuclear organization, and suppressed aging phenotypes. Thus, Non-stop and NIC, supervise EC identity and protects from premature aging.Keywords
Funding Information
- NIH NIGMS (5R35GM118068)
- CDI (MC-II-2014-363)
- Russian Science Foundation (19-74-30026)
- Israel Academy of Sciences and Humanities (719/15)
- Israel Academy of Sciences and Humanities (318/20)
- University of Missouri-Kansas City
- School of Biological Sciences, Washington State University
- University of Missouri-Kansas City (UMKC SEARCH)
- University of Missouri-Kansas City (UMKC SUROP scholars program)
- NIH (ADVANCER)
- Sydney West Translational Cancer Research Centre
- Flinkman-Marandy cancer research grant (AO0001)
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