TY - JOUR
T1 - A non-stop identity complex (Nic) supervises enterocyte identity and protects from premature aging
AU - Neta-Erez,
AU - Israitel, Lena
AU - Bitman-Lotan, Eliya
AU - Wong, Wing Hing
AU - Raz, Gal
AU - Cornelio-Parra, Dayanne V.
AU - Danial, Salwa
AU - Brodsly, Na’Ama Flint
AU - Belova, Elena
AU - Maksimenko, Oksana
AU - Georgiev, Pavel
AU - Druley, Todd
AU - Mohan, Ryan
AU - Orian, Amir
N1 - Funding Information:
We are grateful for mass spectrometry done by Skylar Martin-Brown, Laurence Florens, and Michael P Washburn at the Stowers Institute. We would like to thank Sarah Bray, Adi Salzberg, Bruce Edgar, Jeff Reinitz, Lori Wallrath, Pamela Geyer, Yossi Greenbaum, Lorry Pile, Erika Matunis, Di?az-Benjumea, Mikio Furuse Bas Van-Steensel, Moshe Oren, Joseph Gall, the Bloomington, VDRC, and NIG-FLY Drosophila stock centers for sharing antibodies, fly lines, reagents, and data. This research was supported by: The School of Biological and Chemical Sciences, UMKC; University of Missouri Research Board; UMKC SEARCH, UMKC SUROP scholars programs, and NIH Academic Development Via Applied and Cutting Edge Research (ADVANCER) program; NIGMS grant 5R35GM118068 to RM. Washington University School of Medicine / St. Louis Children?s Hospital Children?s Discovery Institute, MC-II-2014-363 to TD. Russian Science Foundation19-74-30026 to PG, and the Israel Science Foundation (ISF) (Grants 739/15, 318/20), and by the Flinkman Marandi Family cancer research grant to AO.
Funding Information:
Foundation (ISF) (Grants 739/15, 318/20), and by the Flinkman Marandi Family cancer
Funding Information:
This research was supported by: The School of Biological and Chemical Sciences, UMKC;
Publisher Copyright:
© 2021, eLife Sciences Publications Ltd. All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Aging
KW - Cell identity
KW - Drosophila
KW - Gene regulation
KW - Gut
KW - USP22/ Non-stop
KW - Ubiquitin
UR - http://www.scopus.com/inward/record.url?scp=85101929105&partnerID=8YFLogxK
U2 - 10.7554/eLife.62312
DO - 10.7554/eLife.62312
M3 - Article
C2 - 33629655
AN - SCOPUS:85101929105
VL - 10
SP - 1
EP - 52
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e62312
ER -