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<strong>.</strong> 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.
The following sequencing data were deposited: RNAseq and ATAC-seq data are available at NCBI through the Accession number PRJNA657899Link to the the proteomic data set is: The permanent URL to the dataset is: ftp://massive.ucsd.edu/MSV000082625. The data is also accessible from: ProteomeXChange accession: PXD010462 http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD010462. MassIVE | Accession ID: MSV000082625 - ProteomeXchange | Accession ID: PXD010462.
A Non-stop identity complex (NIC) supervises enterocyte identity and protects from pre-mature agingNCBI Bioporject, PRJNA657899.
Expression profiling by array and Genome binding/occupancy profiling by genome tiling array. NCBI GeneNCBI Gene Expression Omnibus, GSE87896.
RNAseq analysis of whole Guts over expressing LaminDm0 or GFP in Enterocytes. NCBI Gene Expression Omnibus.NCBI Gene Expression Omnibus, GSE112640.
- Ryan D Mohan PhD
- Todd Druley
- Pavel Georgiev
- Amir Orian
- Amir Orian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Pankaj Kapahi, Buck Institute for Research on Aging, United States
© 2021, Erez et al.
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