Poly(ADP-ribose) controls DE-cadherin-dependent stem cell maintenance and oocyte localization

Nat Commun. 2012 Mar 27:3:760. doi: 10.1038/ncomms1759.

Abstract

Within the short span of the cell cycle, poly(ADP-ribose) (pADPr) can be rapidly produced by poly(ADP-ribose) polymerases and degraded by poly(ADP-ribose) glycohydrolases. Here we show that changes in association between pADPr and heterogeneous nuclear ribonucleoproteins (hnRNPs) regulate germline stem cell (GSC) maintenance and egg chamber polarity during oogenesis in Drosophila. The association of pADPr and Hrp38, an orthologue of human hnRNPA1, disrupts the interaction of Hrp38 with the 5'-untranslated region of DE-cadherin messenger RNA, thereby diminishing DE-cadherin translation in progenitor cells. Following the reduction of DE-cadherin level, GSCs leave the stem cell niche and differentiate. Defects in either pADPr catabolism or Hrp38 function cause a decrease in DE-cadherin translation, leading to a loss of GSCs and mislocalization of oocytes in the ovary. Taken together, our findings suggest that Hrp38 and its association with pADPr control GSC self-renewal and oocyte localization by regulating DE-cadherin translation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Cycle
  • Cell Differentiation
  • Drosophila / cytology
  • Drosophila / genetics
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Fertility / genetics
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Oocytes
  • Oogenesis* / genetics
  • Ovary / cytology
  • Ovary / metabolism
  • Poly Adenosine Diphosphate Ribose / genetics
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Biosynthesis
  • RNA, Messenger / metabolism
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Signal Transduction / genetics
  • Stem Cells / physiology*

Substances

  • Cadherins
  • Drosophila Proteins
  • HRB98DE protein, Drosophila
  • Heterogeneous-Nuclear Ribonucleoproteins
  • RNA, Messenger
  • Ribonucleoproteins
  • shg protein, Drosophila
  • Poly Adenosine Diphosphate Ribose
  • Poly(ADP-ribose) Polymerases