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Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing.
Cell ( IF 64.5 ) Pub Date : 2018-Mar-22 , DOI: 10.1016/j.cell.2018.02.034
Anthony M Mustoe 1 , Steven Busan 1 , Greggory M Rice 2 , Christine E Hajdin 3 , Brant K Peterson 3 , Vera M Ruda 3 , Neil Kubica 3 , Razvan Nutiu 3 , Jeremy L Baryza 3 , Kevin M Weeks 1
Affiliation  

mRNAs can fold into complex structures that regulate gene expression. Resolving such structures de novo has remained challenging and has limited our understanding of the prevalence and functions of mRNA structure. We use SHAPE-MaP experiments in living E. coli cells to derive quantitative, nucleotide-resolution structure models for 194 endogenous transcripts encompassing approximately 400 genes. Individual mRNAs have exceptionally diverse architectures, and most contain well-defined structures. Active translation destabilizes mRNA structure in cells. Nevertheless, mRNA structure remains similar between in-cell and cell-free environments, indicating broad potential for structure-mediated gene regulation. We find that the translation efficiency of endogenous genes is regulated by unfolding kinetics of structures overlapping the ribosome binding site. We discover conserved structured elements in 35% of UTRs, several of which we validate as novel protein binding motifs. RNA structure regulates every gene studied here in a meaningful way, implying that most functional structures remain to be discovered.

中文翻译:

高分辨率SHAPE探测揭示了mRNA结构的普遍调控功能。

mRNA可以折叠成调节基因表达的复杂结构。从头解决这样的结构仍然具有挑战性,并且限制了我们对mRNA结构的普遍性和功能的理解。我们在活的大肠杆菌细胞中使用SHAPE-MaP实验来获得194个内源转录本的定量,核苷酸分辨率的结构模型,涵盖大约400个基因。单个mRNA具有异常多样的结构,并且大多数包含定义明确的结构。主动翻译会破坏细胞中的mRNA结构。然而,mRNA结构在细胞内和无细胞环境之间仍然相似,这表明结构介导的基因调控具有广阔的潜力。我们发现内源基因的翻译效率是由与核糖体结合位点重叠的结构的展开动力学调节的。我们在35%的UTR中发现了保守的结构化元素,我们验证了其中的几个作为新颖的蛋白质结合基序。RNA结构以有意义的方式调节此处研究的每个基因,这意味着大多数功能结构仍有待发现。
更新日期:2018-03-16
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