Gebauer Fátima, Grskovic Marica, Hentze Matthias W
European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
Mol Cell. 2003 May;11(5):1397-404. doi: 10.1016/s1097-2765(03)00176-x.
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.
抑制雌性果蝇中雄性特异性致死基因2（msl-2）的mRNA翻译对于黑腹果蝇的X染色体剂量补偿至关重要。msl-2的翻译抑制需要性别致死基因（SXL）与该信使RNA的5'和3'非翻译区（UTR）中富含尿苷的序列结合。我们描绘了对SXL调控重要的msl-2 mRNA序列元件，并鉴定了与调控性SXL结合位点相邻的功能关键序列。我们证明，SXL以一种不需要mRNA 5'端存在帽结构的方式抑制翻译起始，并阻止40S核糖体亚基与mRNA的稳定结合。这些结果阐明了黑腹果蝇剂量补偿的一个关键调控步骤。
