Gene Regulation Programme, Centre for Genomic Regulation (CRG) and UPF, 08003 Barcelona, Spain.
RNA. 2012 Jan;18(1):53-64. doi: 10.1261/rna.029603.111. Epub 2011 Nov 18.
Upstream of N-ras (UNR) is a conserved RNA-binding protein that regulates mRNA translation and stability by binding to sites generally located in untranslated regions (UTRs). In Drosophila, sex-specific binding of UNR to msl2 mRNA and the noncoding RNA roX is believed to play key roles in the control of X-chromosome dosage compensation in both sexes. To investigate broader sex-specific functions of UNR, we have identified its RNA targets in adult male and female flies by high-throughput RNA binding and transcriptome analysis. Here we show that UNR binds to a large set of protein-coding transcripts and to a smaller set of noncoding RNAs in a sex-specific fashion. The analyses also reveal a strong correlation between sex-specific binding of UNR and sex-specific differential expression of UTRs in target genes. Validation experiments indicate that UNR indeed recognizes sex-specifically processed transcripts. These results suggest that UNR exploits the transcript diversity generated by alternative processing and alternative promoter usage to bind and regulate target genes in a sex-specific manner.
UNR 位于 N-ras 的上游，是一种保守的 RNA 结合蛋白，通过与通常位于非翻译区（UTR）的位点结合来调节 mRNA 的翻译和稳定性。在果蝇中，UNR 对 msl2 mRNA 和非编码 RNA roX 的性别特异性结合被认为在两性中对 X 染色体剂量补偿的控制中起着关键作用。为了研究 UNR 更广泛的性别特异性功能，我们通过高通量 RNA 结合和转录组分析鉴定了成年雄性和雌性果蝇中的其 RNA 靶标。在这里，我们表明 UNR 以性别特异性的方式结合到一大组编码蛋白的转录本和一小组非编码 RNA。分析还揭示了 UNR 的性别特异性结合与靶基因中 UTR 的性别特异性差异表达之间存在很强的相关性。验证实验表明，UNR 确实可以识别性别特异性加工的转录本。这些结果表明，UNR 利用通过可变剪接和启动子使用产生的转录本多样性，以性别特异性的方式结合和调节靶基因。
