A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging

eLife

Dayanne V Cornelio-Parra¹  Ryan D Mohan¹  Pavel Georgiev²  Elena Belova²  Oksana Maksimenko²  Wing H Wong³  Todd Druley³  Na'ama Flint Brodsly⁴  Salwa Danial⁴  Lena Israitel⁴  Neta Erez⁴  Eliya Bitman-Lotan⁴  Amir Orian⁴  Gal Raz⁴ 

[1] Department of Genetics, Developmental & Evolutionary Biology, School of Biological and Chemical Sciences University of Missouri, Kansas City, United States;Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russian Federation;Division of Pediatric Hematology and Oncology, Washington University, Saint-Louis, United States;Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;

关键词: aging;    cell identity;    gut;    gene regulation;    ubiquitin;    USP22/ Non-stop;   

DOI  :  10.7554/eLife.62312

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown