A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila
A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila
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DOI：
10.1016/j.cell.2005.06.011
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发表时间：
2005-08-26
期刊：
影响因子：
64.5
通讯作者：
Hentze, MW
中科院分区：
文献类型：
--
作者：
Beckmann, K;Grskovic, M;Hentze, MW
果蝇 MSL-2 是剂量补偿复合物的限制成分。雌性果蝇必须抑制 msl-2 mRNA 翻译才能生存，这种抑制是通过与 5' 和 3' 非翻译区 (UTR) 中的位点结合的性致死 (SXL) 介导的。在这里，我们揭示了 SXL 实现翻译起始严格控制的机制。 SXL 与 3'UTR 调节区的结合抑制 43S 核糖体前起始复合物向 mRNA 的募集。逃脱该阻断并与 mRNA 5' 末端结合的核糖体复合物会受到与 5'UTR 结合的 SXL 的攻击，这会干扰对 mRNA 下游起始密码子的扫描。因此，这种故障保护机制形成了剂量补偿关键步骤的分子基础。结果还阐明了通过 mRNA 内多个调控位点进行翻译控制的两步原理。
Drosophila MSL-2 is the limiting component of the dosage compensation complex. Female flies must inhibit msl-2 mRNA translation for survival, and this inhibition is mediated by Sex-lethal (SXL) binding to sites in both the 5' and the 3' untranslated regions (UTRs). Here, we uncover the mechanism by which SXL achieves tight control of translation initiation. SXL binding to the 3'UTR regulatory region inhibits the recruitment of 43S ribosomal preinitiation complexes to the mRNA. Ribosomal complexes escaping this block and binding to the 5' end of the mRNA are challenged by SXL bound to the 5'UTR, which interferes with scanning to the downstream initiation codon of the mRNA. This failsafe mechanism thus forms the molecular basis of a critical step in dosage compensation. The results also elucidate a two step principle of translational control via multiple regulatory sites within an mRNA.