Promoter architecture determines cotranslational regulation of mRNA
Promoter architecture determines cotranslational regulation of mRNA
复制标题
DOI：
10.1101/gr.230458.117
复制
发表时间：
2018-04-01
期刊：
影响因子：
7
通讯作者：
Carey, Lucas B.
中科院分区：
文献类型：
--
作者：
Espinar, Lorena;Schikora Tamarit, Miquel Angel;Carey, Lucas B.
调控基因表达的信息在每个基因中都有编码，但不同的调控区域是否可以单独理解，或者它们是否相互作用，都是未知的。在这里，我们测量了10,000个从诱导启动子或构成启动子转录的开放阅读框架(ORF)的mRNA水平。我们发现，共翻译调控对mRNA水平的强度取决于启动子的结构。通过使用6402个RNA-SEQ实验的新的计算遗传筛选，我们确定RNA解旋酶Dbp2是针对可诱导启动子的共翻译调节被减少的机制。最后，我们发现，对于构成基因，而不是诱导基因，编码对生长速度变化反应的mRNA水平调节的大部分信息是在ORF中编码的，而不是在启动子中。因此，ORF序列是基因表达的主要调节因子，启动子和ORF之间的非线性相互作用决定了mRNA水平。
Information that regulates gene expression is encoded throughout each gene but if different regulatory regions can be understood in isolation, or if they interact, is unknown. Here we measure mRNA levels for 10,000 open reading frames (ORFs) transcribed from either an inducible or constitutive promoter. We find that the strength of cotranslational regulation on mRNA levels is determined by promoter architecture. By using a novel computational genetic screen of 6402 RNA-seq experiments, we identify the RNA helicase Dbp2 as the mechanism by which cotranslational regulation is reduced specifically for inducible promoters. Finally, we find that for constitutive genes, but not inducible genes, most of the information encoding regulation of mRNA levels in response to changes in growth rate is encoded in the ORF and not in the promoter. Thus, the ORF sequence is a major regulator of gene expression, and a nonlinear interaction between promoters and ORFs determines mRNA levels.