title: Translational control of dosage compensation in Drosophila by Sex-lethal: cooperative silencing via the 5' and 3' UTRs of msl-2 mRNA is independent of the poly(A) tail.
abstract: Translational repression of male-specific-lethal 2 (msl-2) mRNA by Sex-lethal (SXL) controls dosage compensation in Drosophila. In vivo regulation involves cooperativity between SXL-binding sites in the 5' and 3' untranslated regions (UTRs). To investigate the mechanism of msl-2 translational control, we have developed a novel cell-free translation system from Drosophila embryos that recapitulates the critical features of mRNA translation in eukaryotes: cap and poly(A) tail dependence. Importantly, tight regulation of msl-2 translation in this system requires cooperation between the SXL-binding sites in both the 5' and 3' UTRs, as seen in vivo. However, in contrast to numerous other developmentally regulated mRNAs, the regulation of msl-2 mRNA occurs by a poly(A) tail-independent mechanism. The approach described here allows mechanistic analysis of translational control in early Drosophila development and has revealed insights into the regulation of dosage compensation by SXL.
authors.affiliation: European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Gebauer
authors.forename: D F
authors.initials: DF
authors.lastname: Corona
authors.forename: T
authors.initials: T
authors.lastname: Preiss
authors.forename: P B
authors.initials: PB
authors.lastname: Becker
authors.forename: M W
authors.initials: MW
authors.lastname: Hentze
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004268:DNA-Binding Proteins; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000235:genetics*; D011061:Poly A / Q000235:genetics; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C067777:Sxl protein, Drosophila; D014157:Transcription Factors; C094166:msl-2 protein, Drosophila; D011061:Poly A