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锌反应元件 Slc39a5（Zip5）翻译的调控是由 3'非翻译区的保守元件介导的。

Regulation of zinc-responsive Slc39a5 (Zip5) translation is mediated by conserved elements in the 3'-untranslated region.

机构信息

Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7421, USA.

出版信息

Biometals. 2012 Apr;25(2):319-35. doi: 10.1007/s10534-011-9508-4. Epub 2011 Nov 24.

DOI:10.1007/s10534-011-9508-4
PMID:22113231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3299966/
Abstract

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.

摘要

锌缺乏时基底外侧锌转运蛋白 ZIP5 的翻译受到抑制，但 Zip5 mRNA 仍与多核糖体结合，并且当锌得到补充时可以快速翻译。在此，我们研究了调节 Zip5 翻译的机制。Zip5 mRNA 的 3'非翻译区（UTR）在哺乳动物中高度保守，并且 mFOLD 预测它形成非常稳定的茎环结构。三种算法预测该结构的侧翼是 miR-328 和 miR-193a 的重复种子位点。RNAse 足迹支持这样一种观点，即在该 3'-UTR 中存在稳定的茎环结构，并且电泳迁移率变动分析检测到多核糖体蛋白特异性结合到 Zip5 3'-UTR 中的茎环结构。miR-328 和 miR-193a 在已知调节锌可用性响应下 Zip5 mRNA 翻译的组织中表达，并且都与多核糖体相关，与 Zip5 mRNA 的定位一致。使用克隆到荧光素酶 cDNA 3'末端的天然和突变 Zip5 3'-UTR 的瞬时转染实验表明，miRNA 种子位点和茎环一起协同作用，在锌得到补充时增强 Zip5 mRNA 的翻译。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/e3ceee9fadc7/10534_2011_9508_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/e615350e5fb4/10534_2011_9508_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/d2b334f228d6/10534_2011_9508_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/9355f77dbe9c/10534_2011_9508_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/d1e76203552b/10534_2011_9508_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/5a4e28146592/10534_2011_9508_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/8e0287be6b86/10534_2011_9508_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/3e28f17f08e5/10534_2011_9508_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/e3ceee9fadc7/10534_2011_9508_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/e615350e5fb4/10534_2011_9508_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/d2b334f228d6/10534_2011_9508_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/9355f77dbe9c/10534_2011_9508_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/d1e76203552b/10534_2011_9508_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/5a4e28146592/10534_2011_9508_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/8e0287be6b86/10534_2011_9508_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/3e28f17f08e5/10534_2011_9508_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74fa/3299966/e3ceee9fadc7/10534_2011_9508_Fig8_HTML.jpg

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