Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing.
Pervasive Regulatory Functions of mRNA Structure Revealed by High-Resolution SHAPE Probing.
复制标题
DOI：
10.1016/j.cell.2018.02.034
复制
发表时间：
2018-03-22
期刊：
影响因子：
64.5
通讯作者：
Weeks KM
中科院分区：
文献类型：
--
作者：
Mustoe AM;Busan S;Rice GM;Hajdin CE;Peterson BK;Ruda VM;Kubica N;Nutiu R;Baryza JL;Weeks KM
信使RNA（mRNA）可以折叠成调节基因表达的复杂结构。从头解析这些结构仍然具有挑战性，并且对mRNA结构的流行和功能的理解有限。我们在活体E.大肠杆菌细胞，以获得194个内源性转录物，包括约400个基因的定量，核苷酸分辨率的结构模型。单个mRNA具有异常多样的结构，并且大多数包含明确定义的结构。主动翻译使细胞中的mRNA结构不稳定。然而，mRNA结构在细胞内和无细胞环境之间保持相似，表明结构介导的基因调控的广泛潜力。我们发现，内源基因的翻译效率是由重叠的核糖体结合位点的结构的展开动力学调节。我们在35%的非翻译区发现了保守的结构元件，其中一些我们验证为新的蛋白质结合基序。RNA结构以一种有意义的方式调控着这里研究的每一个基因，这意味着大多数功能结构仍有待发现。高分辨率探测活E.大肠杆菌细胞揭示了细菌mRNA折叠成高度多样和复杂的结构，并且这些结构具有广泛的调节功能。
Messenger RNAs (mRNAs) can fold into complex structures that regulate gene expression. Resolving such structures de novo has remained challenging and has limited 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 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 untranslated regions, 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. High-resolution probing of hundreds of genes in living E. coli cells reveals that bacterial mRNAs fold into highly diverse and complex structures, and that these structures have widespread regulatory functions.
登录
查看更多内容
影响因子：
14.9
作者：
Espah Borujeni A;Cetnar D;Farasat I;Smith A;Lundgren N;Salis HM
通讯作者：
Salis HM
影响因子：
4.5
作者：
Del Campo C;Bartholomäus A;Fedyunin I;Ignatova Z
通讯作者：
Ignatova Z
影响因子：
9.9
作者：
Bentele, Kajetan;Saffert, Paul;Bluethgen, Nils
通讯作者：
Bluethgen, Nils
影响因子：
14.9
作者：
DONLY, BC;MACKIE, GA
通讯作者：
MACKIE, GA
DOI：
10.1073/pnas.0806929106
发表时间：
2009-01-06
影响因子：
11.1
作者：
Deigan, Katherine E.;Li, Tian W.;Weeks, Kevin M.
通讯作者：
Weeks, Kevin M.