Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3′ UTR:: translational repression for dosage compensation
Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3′ UTR:: translational repression for dosage compensation
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DOI：
10.1101/gad.371406
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发表时间：
2006-02-01
影响因子：
10.5
通讯作者：
Hentze, MW
中科院分区：
文献类型：
--
作者：
Duncan, K;Grskovic, M;Hentze, MW
MSL-2(雄性特异性致死2)是果蝇剂量补偿复合体(DCC)的限制性成分，它特异性地增加雄性X染色体的转录。MSL-2蛋白在雌性中的异位表达导致X染色体上的DCC组装和致死性。抑制MSL-2的合成需要雌性特异性蛋白性致死(SXL)，它与msl-2mRNA5‘和3’非翻译区(UTRs)结合，通过不同的UTR特异性机制阻止翻译。在这里，我们纯化了翻译沉默的MS1-2 mRNP，并确定UNR(N-ras的上游)是SXL招募到3‘UTR的蛋白质。我们证明SXL需要UNR作为3‘-UTR介导的调节的辅阻遏物，赋予普遍表达的UNR蛋白女性特有的功能。我们的结果揭示了UNR作为翻译抑制物的一个新的功能角色，并表明UNR是“故障安全”剂量补偿调节系统的关键组成部分，该系统防止雌性细胞中有毒的MSL-2合成。
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 ms1-2 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.