Drosophila sex-lethal inhibits the stable association of the 40S ribosomal subunit with msl-2 mRNA.
The inhibition of male-specific lethal-2 (msl-2) mRNA translation in female flies is essential for X chromosome dosage compensation in Drosophila melanogaster. Translational repression of msl-2 requires sex-lethal (SXL) binding to uridine-rich sequences in both the 5' and 3' untranslated regions (UTRs) of the message. We delineate the msl-2 mRNA sequence elements that are important for regulation by SXL and identify functionally critical sequences adjacent to regulatory SXL binding sites. We demonstrate that SXL inhibits translation initiation and prevents the stable association of the 40S ribosomal subunit with the mRNA in a manner that does not require the presence of a cap structure at the 5' end of the mRNA. These results elucidate a critical regulatory step for dosage compensation in Drosophila melanogaster.
Gebauer
Fátima
F
European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Grskovic
Marica
M
Hentze
Matthias W
MW
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; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics*; D005260:Female; D005804:Genes, Lethal / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D039381:RNA Cap-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C067777:Sxl protein, Drosophila; D014157:Transcription Factors; C094166:msl-2 protein, Drosophila