A non-stop identity complex (Nic) supervises enterocyte identity and protects from premature aging

Neta-Erez, Lena Israitel, Eliya Bitman-Lotan, Wing Hing Wong, Gal Raz, Dayanne V. Cornelio-Parra, Salwa Danial, Na’Ama Flint Brodsly, Elena Belova, Oksana Maksimenko, Pavel Georgiev, Todd Druley, Ryan Mohan, Amir Orian

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article numbere62312
Pages (from-to)1-52
Number of pages52
JournaleLife
Volume10
DOIs
StatePublished - Feb 2021

Keywords

  • Aging
  • Cell identity
  • Drosophila
  • Gene regulation
  • Gut
  • USP22/ Non-stop
  • Ubiquitin

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