Conserved regions of the DMD 3' UTR regulate translation and mRNA abundance in cultured myotubes.
Conserved regions of the DMD 3' UTR regulate translation and mRNA abundance in cultured myotubes.
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DOI：
10.1016/j.nmd.2014.05.006
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发表时间：
2014-08
影响因子：
2.8
通讯作者：
Howard, Michael T.
中科院分区：
文献类型：
--
作者：
Larsen, C. Aaron;Howard, Michael T.
杜氏肌营养不良症（DMD）是一种严重的肌肉萎缩性疾病，是由DMD基因突变引起的，该基因编码肌营养不良蛋白。其调节具有治疗意义，因为即使功能性肌营养不良蛋白表达的微小变化也会显著影响DMD的严重程度。虽然几种DMD mRNA亚型的组织特异性分布和转录调控已得到很好的表征，但抗肌萎缩蛋白合成的转录后调控尚未得到很好的理解。在这里，我们利用qRTPCR和定量双荧光素酶报告基因测定来检查亚型特异性DMD 5'UTR和高度保守的DMD 3' UTR对C2C12细胞中mRNA丰度和基因表达的翻译控制的影响。5'UTR显示在成肌细胞和肌管中以低效率启动翻译。然而，在3'UTR中的两个大的高度保守元件，其与先前描述的Lemaire A和D区重叠，在成肌细胞分化成肌管时增加mRNA水平并增强翻译。本文的结果暗示DMD UTR在肌营养不良蛋白表达中的重要作用，并描绘了DMD 3' UTR中发现的稳态mRNA水平和翻译增强子活性的肌管特异性调节所需的顺式作用元件。
Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease, is caused by mutations in the DMD gene, which encodes for the protein dystrophin. Its regulation is of therapeutic interest as even small changes in expression of functional dystrophin can significantly impact the severity of DMD. While tissue-specific distribution and transcriptional regulation of several DMD mRNA isoforms has been well characterized, the post-transcriptional regulation of dystrophin synthesis is not well understood. Here, we utilize qRTPCR and a quantitative dual-luciferase reporter assay to examine the effects of isoform specific DMD 5’ UTRs and the highly conserved DMD 3’ UTR on mRNA abundance and translational control of gene expression in C2C12 cells. The 5’ UTRs were shown to initiate translation with low efficiency in both myoblasts and myotubes. Whereas, two large highly conserved elements in the 3’ UTR, which overlap the previously described Lemaire A and D regions, increase mRNA levels and enhance translation upon differentiation of myoblasts into myotubes. The results presented here implicate an important role for DMD UTRs in dystrophin expression and delineate the cis-acting elements required for the myotube-specific regulation of steady-state mRNA levels and translational enhancer activity found in the DMD 3’ UTR.
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影响因子：
3.7
作者：
Bovolenta M;Erriquez D;Valli E;Brioschi S;Scotton C;Neri M;Falzarano MS;Gherardi S;Fabris M;Rimessi P;Gualandi F;Perini G;Ferlini A
通讯作者：
Ferlini A
影响因子：
158.5
作者：
Goemans, Nathalie M.;Tulinius, Mar;van Deutekom, Judith C.
通讯作者：
van Deutekom, Judith C.
影响因子：
5.2
作者：
de Brouwer, Arjan P. M.;Nabuurs, Sander B.;Kleefstra, Tjitske
通讯作者：
Kleefstra, Tjitske
通过未翻译基因区域和其他非编码元件调节真核基因表达。
影响因子：
8
作者：
Barrett, Lucy W.;Fletcher, Sue;Wilton, Steve D.
通讯作者：
Wilton, Steve D.
影响因子：
168.9
作者：
Cirak, Sebahattin;Arechavala-Gomeza, Virginia;Guglieri, Michela;Feng, Lucy;Torelli, Silvia;Anthony, Karen;Abbs, Stephen;Garralda, Maria Elena;Bourke, John;Wells, Dominic J.;Dickson, George;Wood, Matthew J. A.;Wilton, Steve D.;Straub, Volker;Kole, Ryszard;Shrewsbury, Stephen B.;Sewry, Caroline;Morgan, Jennifer E.;Bushby, Kate;Muntoni, Francesco
通讯作者：
Muntoni, Francesco