title: Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3' UTR: translational repression for dosage compensation.
abstract: MSL-2 (male-specific lethal 2) is the limiting component of the Drosophila dosage compensation complex (DCC) that specifically increases transcription from the male X chromosome. Ectopic expression of MSL-2 protein in females causes DCC assembly on both X chromosomes and lethality. Inhibition of MSL-2 synthesis requires the female-specific protein sex-lethal (SXL), which binds to the msl-2 mRNA 5' and 3' untranslated regions (UTRs) and blocks translation through distinct UTR-specific mechanisms. Here, we purify translationally silenced msl-2 mRNPs and identify UNR (upstream of N-ras) as a protein recruited to the 3' UTR by SXL. We demonstrate that SXL requires UNR as a corepressor for 3'-UTR-mediated regulation, imparting a female-specific function to the ubiquitously expressed UNR protein. Our results reveal a novel functional role for UNR as a translational repressor and indicate that UNR is a key component of a "fail-safe" dosage compensation regulatory system that prevents toxic MSL-2 synthesis in female cells.
authors.affiliation: Gene Expression Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors.forename: Kent
authors.initials: K
authors.lastname: Duncan
authors.forename: Marica
authors.initials: M
authors.lastname: Grskovic
authors.forename: Claudia
authors.initials: C
authors.lastname: Strein
authors.forename: Karsten
authors.initials: K
authors.lastname: Beckmann
authors.forename: Ricarda
authors.initials: R
authors.lastname: Niggeweg
authors.forename: Irina
authors.initials: I
authors.lastname: Abaza
authors.forename: Fátima
authors.initials: F
authors.lastname: Gebauer
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilm
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D004303:Dosage Compensation, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C067777:Sxl protein, Drosophila; D014157:Transcription Factors; C509278:UNR protein, Drosophila; C026452:messenger ribonucleoprotein; C094166:msl-2 protein, Drosophila