title: Three RNA binding proteins form a complex to promote differentiation of germline stem cell lineage in Drosophila.
abstract: In regenerative tissues, one of the strategies to protect stem cells from genetic aberrations, potentially caused by frequent cell division, is to transiently expand the stem cell daughters before further differentiation. However, failure to exit the transit amplification may lead to overgrowth, and the molecular mechanism governing this regulation remains vague. In a Drosophila mutagenesis screen for factors involved in the regulation of germline stem cell (GSC) lineage, we isolated a mutation in the gene CG32364, which encodes a putative RNA-binding protein (RBP) and is designated as tumorous testis (tut). In tut mutant, spermatogonia fail to differentiate and over-amplify, a phenotype similar to that in mei-P26 mutant. Mei-P26 is a TRIM-NHL tumor suppressor homolog required for the differentiation of GSC lineage. We found that Tut binds preferentially a long isoform of mei-P26 3'UTR, and is essential for the translational repression of mei-P26 reporter. Bam and Bgcn are both RBPs that have also been shown to repress mei-P26 expression. Our genetic analyses indicate that tut, bam, or bgcn is required to repress mei-P26 and to promote the differentiation of GSCs. Biochemically, we demonstrate that Tut, Bam, and Bgcn can form a physical complex in which Bam holds Tut on its N-terminus and Bgcn on its C-terminus. Our in vivo and in vitro evidence illustrate that Tut acts with Bam, Bgcn to accurately coordinate proliferation and differentiation in Drosophila germline stem cell lineage.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China,; The University of Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China,; The University of Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Chan
authors.initials: C
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China,; The University of Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China,; The University of Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China,; The University of Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China,; The University of Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P.R. China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D004331:Drosophila melanogaster; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005854:Germ Cells / Q000166:cytology; D006801:Humans; D008297:Male; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
chemical_list: D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C000602551:Tut protein, Drosophila; C091674:bam protein, Drosophila; D004265:DNA Helicases; C414082:bgcn protein, Drosophila