Regulation of zinc-responsive Slc39a5 (Zip5) translation is mediated by conserved elements in the 3'-untranslated region.
Regulation of zinc-responsive Slc39a5 (Zip5) translation is mediated by conserved elements in the 3'-untranslated region.
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DOI：
10.1007/s10534-011-9508-4
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发表时间：
2012-04
期刊：
影响因子：
3.5
通讯作者：
Andrews, Glen K.
中科院分区：
文献类型：
--
作者：
Weaver, Benjamin P.;Andrews, Glen K.
基底外侧锌转运体ZIP 5的翻译在锌缺乏期间被抑制，但ZIP 5 mRNA仍然与多聚核糖体相关，并且当锌被补充时可以被快速翻译。在此，我们研究了Zip 5的翻译调控机制。Zip 5 mRNA的3′-非翻译区（UTR）在哺乳动物中是高度保守的，并且通过mFOLD预测形成非常稳定的茎环结构。三种算法预测该结构侧翼为miR-328和miR-193 a的重复种子位点。RNA酶足迹法支持在该3′-UTR中存在稳定的茎环结构的观点，并且电泳迁移率变动测定检测特异性结合至Zip 5 3′-UTR中的茎环结构的多核糖体蛋白。miR-328和miR-193 a在已知响应锌可用性调节Zip 5 mRNA翻译的组织中表达，并且两者都是与Zip 5 mRNA定位一致的多核糖体相关的。使用天然和突变的Zip 5 3′-UTR克隆到荧光素酶cDNA的瞬时转染试验显示，当锌充足时，miRNA种子位点和茎环共同起作用以增加Zip 5 mRNA的翻译。本文的在线版本（doi：10.1007/s10534-011-9508-4）包含补充材料，可供授权用户使用。
Translation of the basolateral zinc transporter ZIP5 is repressed during zinc deficiency but Zip5 mRNA remains associated with polysomes and can be rapidly translated when zinc is repleted. Herein, we examined the mechanisms regulating translation of Zip5. The 3′-untranslated region (UTR) of Zip5 mRNA is well conserved among mammals and is predicted by mFOLD to form a very stable stem-loop structure. Three algorithms predict this structure to be flanked by repeated seed sites for miR-328 and miR-193a. RNAse footprinting supports the notion that a stable stem-loop structure exists in this 3′-UTR and electrophoretic mobility shift assays detect polysomal protein(s) binding specifically to the stem-loop structure in the Zip5 3′-UTR. miR-328 and miR-193a are expressed in tissues known to regulate Zip5 mRNA translation in response to zinc availability and both are polysome-associated consistent with Zip5 mRNA localization. Transient transfection assays using native and mutant Zip5 3′-UTRs cloned 3′ to luciferase cDNA revealed that the miRNA seed sites and the stem-loop function together to augment translation of Zip5 mRNA when zinc is replete. The online version of this article (doi:10.1007/s10534-011-9508-4) contains supplementary material, which is available to authorized users.
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影响因子：
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DOI：
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发表时间：
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DOI：
10.1073/pnas.0800650105
发表时间：
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影响因子：
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