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Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila (RNA-Binding Proteins and Germline Differentiation)

Chen, Di ; Wu, Chan ; Zhao, Shaowei ; Geng, Qing ; Gao, Yu ; Li, Xin ; Zhang, Yang ; Wang, Zhaohui; Fuller, Margaret T. (Editor)

2014, Vol.10(11), p.e1004797 [Tạp chí có phản biện]

ISSN: 1553-7390 ; E-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1004797

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  • Nhan đề:
    Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila (RNA-Binding Proteins and Germline Differentiation)
  • Tác giả: Chen, Di ; Wu, Chan ; Zhao, Shaowei ; Geng, Qing ; Gao, Yu ; Li, Xin ; Zhang, Yang ; Wang, Zhaohui
  • Fuller, Margaret T. (Editor)
  • Chủ đề: Research Article ; Biology And Life Sciences
  • Là 1 phần của: 2014, Vol.10(11), p.e1004797
  • Mô tả: 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. ; In regenerative tissues, the successive differentiation of stem cell lineage is well controlled and coordinated with proper cell proliferation at each differentiation stage. Disruption of the control mechanism can lead to tumor growth or tissue degeneration. The germline stem cell lineage of spermatogenesis provides an ideal research model to unravel the genetic network coordinating proliferation and differentiation. In a genetic screen, we identified a male-sterile mutant whose germ cells are under-differentiated and overproliferating. The responsible gene encodes an RNA-binding protein whose target belongs to a tumor suppressor family. We demonstrate that this and two other RNA-binding proteins form a physical and functional unit to ensure the proper differentiation and accurate proliferation of germline stem cell lineage.
  • Ngôn ngữ: English
  • Số nhận dạng: ISSN: 1553-7390 ; E-ISSN: 1553-7404 ; DOI: 10.1371/journal.pgen.1004797

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