Three RNA binding proteins form a complex to promote differentiation of germline stem cell lineage in Drosophila

PLoS Genet. 2014 Nov 20;10(11):e1004797. doi: 10.1371/journal.pgen.1004797. eCollection 2014 Nov.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cell Proliferation / genetics
  • DNA Helicases / biosynthesis
  • DNA Helicases / genetics*
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster
  • Female
  • Gene Expression Regulation / genetics
  • Germ Cells / cytology
  • Humans
  • Male
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Stem Cells / cytology

Substances

  • Drosophila Proteins
  • RNA-Binding Proteins
  • Tut protein, Drosophila
  • bam protein, Drosophila
  • DNA Helicases
  • bgcn protein, Drosophila

Grant support

This study was supported by National Key Basic Research Program of China (2013CB945000) and National Science Foundation China (31271539). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.