Understanding the interconnection between mRNA turnover and mRNA translation

了解 mRNA 周转和 mRNA 翻译之间的相互关系

• 批准号: 8506450
• 负责人: Jeffery Coller
• 金额: $ 31.39万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8506450
• 关键词: Address; Affect; Biological Assay; Cells; Complex; Coupled; Coupling; Cues; Cytoplasmic Structures; DNA; Data; Defect; Digestion; Dissociation; Ensure; Enzymes; Event; Excision; Failure; Free Ribosome; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genetic; Genetic Translation; Genomics; Grant; Health; Heterogeneity; Human; In Vitro; Lead; Learning; Maps; Mediating; Messenger RNA; Molecular; Movement; Nuclear; Output; Pathway interactions; Poly A; Poly(A) Tail; Process; Protein Biosynthesis; Proteins; Publishing; RNA; Recruitment Activity; Regulation; Ribosomes; Role; Signal Transduction; Specificity; Staging; Structure; Substrate Specificity; System; Tail; Testing; Transcript; Translation Initiation; Translations; Work; abstracting; design; mRNA Decay; mRNA decapping; malformation; malignant neurologic neoplasms; member; poly A specific exoribonuclease; polyadenosine; polyadenylated messenger RNA; public health relevance; reconstitution; response

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.

描述(由申请人提供)： 摘要本研究的重点是信使核糖核酸的去帽和去烯化。去帽是去除5‘端帽子结构的重要一步，是对mRNA的调控。信使核糖核酸的周转与蛋白质合成过程密切相关。重要的是，这项拨款的工作证明，破坏mRNAs的因素本身就是核糖体功能的调节器。具体地说，去壳复合体的一个关键成分DHH1减缓了核糖体的移位，这一事件有助于刺激5‘帽的去除和转录体的降解。这项资助的第一个目的是为了了解DHH1如何改变核糖体功能。这项建议还侧重于mRNA的死烯基化。去腺苷酸化是去掉信使核糖核酸上的3‘聚(A)尾巴，在信使核糖核酸发生去核糖核酸之前是必需的。这笔赠款的目标2侧重于了解死烯基化和去封端是如何耦合的。去腺苷也被认为是信使核糖核酸周转的限速步骤。重要的是，去烯化速率在不同的信使核糖核酸物种之间是不同的，但这些异质性是如何实现的还不清楚。本提案的目的3是确定不同的去烯化速率是如何发生的。总而言之，这些目的突出了去壳层和死烯基酶在控制各种基因表达事件中的重要性。