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

• DOI: 10.1242/dev.134247
• Publication Date: 2016-07-29T00:38:56Z
• Authors: Jun Yu; Xiang Lan; Xia Chen; Chao Yu; Yiwen Xu; Yujuan Liu; Lingna Xu; Heng-Yu Fan; Chao Tong
• Keywords: Male; 0301 basic medicine; RNA Splicing; Stem Cells; Ubiquitin-Protein Ligase Complexes; Cell Differentiation; 3. Good health; 03 medical and health sciences; Testis; Animals; Drosophila Proteins; Drosophila; RNA, Messenger; Cell Self Renewal; Signal Transduction

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.