A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging
Neta Erez,
Lena Israitel,
Eliya Bitman-Lotan,
Wing H Wong,
Gal Raz,
Dayanne V Cornelio-Parra,
Salwa Danial,
Na'ama Flint Brodsly,
Elena Belova,
Oksana Maksimenko,
Pavel Georgiev,
Todd Druley,
Ryan D Mohan,
Amir Orian
Affiliations
Neta Erez
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Lena Israitel
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Eliya Bitman-Lotan
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Wing H Wong
Division of Pediatric Hematology and Oncology, Washington University, Saint-Louis, United States
Gal Raz
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Dayanne V Cornelio-Parra
Department of Genetics, Developmental & Evolutionary Biology, School of Biological and Chemical Sciences University of Missouri, Kansas City, United States
Salwa Danial
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Na'ama Flint Brodsly
Rappaport Research Institute and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Elena Belova
Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russian Federation
Oksana Maksimenko
Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russian Federation
Pavel Georgiev
Department of the Control of Genetic Processes, Institute of Gene Biology Russian Academy of Sciences, Moscow, Russian Federation
Todd Druley
Division of Pediatric Hematology and Oncology, Washington University, Saint-Louis, United States
Department of Genetics, Developmental & Evolutionary Biology, School of Biological and Chemical Sciences University of Missouri, Kansas City, United States
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.
