Dazl binds in vivo to specific transcripts and can regulate the pre-meiotic translation of Mvh in germ cells.
Gametogenesis is a complex process subject to strict controls at both levels of transcription and translation. Members of a family of conserved RNA-binding proteins encoded by the DAZ genes are required for the translational regulation of gene expression essential for this process. Although loss of DAZ family genes is associated with infertility in several organisms including humans, the identity of the transcripts regulated in vivo is unknown. Using a combination of immunoprecipitation and microarray analysis, we have identified a number of mRNAs that are bound by the murine Dazl protein both in vivo and in vitro. Sequence analysis shows that these transcripts contain binding sites for Dazl, which have been conserved during evolution between human, rat and mouse. We have focussed on mouse vasa homologue (Mvh), a gene that is essential for male gametogenesis, and show that Dazl stimulates translation via the Mvh 3'-UTR. Finally, we show that germ cells of Dazl null mice contain reduced levels of Mvh protein, indicating that Dazl-mediated regulation of Mvh translation is crucial for mammalian spermatogenesis.
Reynolds
Nicola
N
MRC Human Genetics Unit, Western General Hospital, University of Edinburgh, UK.
Collier
Brian
B
Maratou
Klio
K
Bingham
Victoria
V
Speed
Robert M
RM
Taggart
Mary
M
Semple
Colin A
CA
Gray
Nicola K
NK
Cooke
Howard J
HJ
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases; D005260:Female; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013094:Spermatozoa / Q000502:physiology*; D014158:Transcription, Genetic; D014982:Xenopus laevis
D020413:3' Untranslated Regions; C101358:DAZL protein, human; C508515:DAZL protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C090864:Ddx4 protein, mouse; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases