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Publication : Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes.

First Author  Yu J Year  2016
Journal  Development Volume  143
Issue  16 Pages  2930-45
PubMed ID  27471256 Mgi Jnum  J:302718
Mgi Id  MGI:6509510 Doi  10.1242/dev.134247
Citation  Yu J, et al. (2016) Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes. Development 143(16):2930-45
abstractText  The homeostasis of self-renewal and differentiation in stem cells is controlled by intrinsic signals and their niche. We conducted a large-scale RNA interference (RNAi) screen in Drosophila testes and identified 221 genes required for germline stem cell (GSC) maintenance or differentiation. Knockdown of these genes in transit-amplifying spermatogonia and cyst cells further revealed various phenotypes. Complex analysis uncovered that many of the identified genes are involved in key steps of protein synthesis and degradation. A group of genes that are required for mRNA splicing and protein translation contributes to both GSC self-renewal and early germ cell differentiation. Loss of genes in the protein degradation pathway in cyst cells leads to testis tumors consisting of overproliferated germ cells. Importantly, in the Cullin 4-RING E3 ubiquitin ligase (CRL4) complex, we identified multiple proteins that are crucial to GSC self-renewal: pic/DDB1, a CRL4 linker protein, is not only required for GSC self-renewal in flies but also for maintenance of spermatogonial stem cells (SSCs) in mice.
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