title: Temporally regulated traffic of HuR and its associated ARE-containing mRNAs from the chromatoid body to polysomes during mouse spermatogenesis.
abstract: BACKGROUND
  In mammals, a temporal disconnection between mRNA transcription and protein synthesis occurs during late steps of germ cell differentiation, in contrast to most somatic tissues where transcription and translation are closely linked. Indeed, during late stages of spermatogenesis, protein synthesis relies on the appropriate storage of translationally inactive mRNAs in transcriptionally silent spermatids. The factors and cellular compartments regulating mRNA storage and the timing of their translation are still poorly understood. The chromatoid body (CB), that shares components with the P. bodies found in somatic cells, has recently been proposed to be a site of mRNA processing. Here, we describe a new component of the CB, the RNA binding protein HuR, known in somatic cells to control the stability/translation of AU-rich containing mRNAs (ARE-mRNAs).
  
  
  RESULTS
  Using a combination of cell imagery and sucrose gradient fractionation, we show that HuR localization is highly dynamic during spermatid differentiation. First, in early round spermatids, HuR colocalizes with the Mouse Vasa Homolog, MVH, a marker of the CB. As spermatids differentiate, HuR exits the CB and concomitantly associates with polysomes. Using computational analyses, we identified two testis ARE-containing mRNAs, Brd2 and GCNF that are bound by HuR and MVH. We show that these target ARE-mRNAs follow HuR trafficking, accumulating successively in the CB, where they are translationally silent, and in polysomes during spermatid differentiation.
  
  
  CONCLUSIONS
  Our results reveal a temporal regulation of HuR trafficking together with its target mRNAs from the CB to polysomes as spermatids differentiate. They strongly suggest that through the transport of ARE-mRNAs from the CB to polysomes, HuR controls the appropriate timing of ARE-mRNA translation. HuR might represent a major post-transcriptional regulator, by promoting mRNA storage and then translation, during male germ cell differentiation.
authors.affiliation: CBD, CNRS UMR5547, IFR 109, Université Paul Sabatier, Toulouse, France.
authors.forename: Mai
authors.initials: M
authors.lastname: Nguyen Chi
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
authors.forename: Eric
authors.initials: E
authors.lastname: Agius
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vanzo
authors.forename: Khalid S A
authors.initials: KS
authors.lastname: Khabar
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.forename: Dominique
authors.initials: D
authors.lastname: Morello