Understanding the interconnection between mRNA turnover and mRNA translation

描述（由申请人提供）： 摘要本论文主要研究mRNA的去帽和去腺苷化。去帽是去除5'帽结构是mRNA调控中的重要步骤。mRNA的周转与蛋白质合成过程密切相关。重要的是，这项资助的工作证明了参与破坏mRNA的因子本身就是核糖体功能的调节因子。具体地，称为DHH1的脱帽复合物的关键组分减缓核糖体易位，并且该事件用于刺激5'帽的去除和转录体的降解。该基金的第一个目的是了解DHH1如何改变核糖体功能。该提议还关注mRNA的去腺苷化。脱腺苷酸化是去除mRNA上的3' poly（A）尾，并且在mRNA脱帽之前是必需的。该基金的目标2侧重于了解去腺苷化和去帽化是如何耦合的。脱腺苷酸化也被认为是mRNA周转的限速步骤。重要的是，去腺苷化速率在mRNA物种之间是可变的，但这些异质性是如何实现的尚不清楚。本提案的目的3是确定差异去腺苷化速率如何发生。总之，这些目的突出了去帽酶和去腺苷酶在控制基因表达事件的多样性中的重要性。

DESCRIPTION (provided by applicant): Abstract This proposal focuses on the decapping and deadenylation of mRNA. Decapping is the removal of the 5' cap structure is an important step in the regulation of mRNA. The turnover of mRNA is intimately connected to the process of protein synthesis. Importantly, work from this grant has documented that factors involved in destroying mRNAs are themselves regulators of ribosome function. Specifically, a key component of the decapping complex called DHH1 slows ribosome translocation and this event serves to stimulate removal of the 5' cap and degradation of the transcript body. The first Aim of this grant is designed to understand how DHH1 alters ribosome function. This proposal also focuses on deadenylation of mRNA. Deadenylation is the removal of the 3' poly(A) tail on an mRNA and required before mRNA decapping can occur. Aim 2 of this grant focuses on understanding how deadenylation and decapping are coupled. Deadenylation is also thought to be the rate-limiting step in mRNA turnover. Importantly, deadenylation rates are variable between mRNA species but how these heterogeneity is achieved is unclear. Aim 3 of this proposal is to determine how differential deadenylation rates occur. Together, these Aims highlight the importance of the decapping and deadenylase enzymes in controlling a diversity of gene expression events.