5’ end RNA Caps in Gene Expression

基因表达中的 5 端 RNA 帽

• 批准号: 10622778
• 负责人: MEGERDITCH KILEDJIAN
• 金额: $ 35.55万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622778
• 关键词: Adenine; Cells; DNA; Diphosphates; Disease; Elements; Excision; Flavin-Adenine Dinucleotide; Gene Expression; Gene Silencing; Guanosine; Homeostasis; Individual; Link; Messenger RNA; Metabolism; Minor; Molecular; Niacinamide; Nucleotides; Physiological; RNA; RNA Caps; RNA Decay; RNA Stability; RNA metabolism; Regulation; Translations; Uridine Diphosphate N-Acetylglucosamine; Work; clinical phenotype; genetic information; insight; mRNA Stability; novel; therapeutic RNA; transmission process

Project Summary The proposed studies are focused on our long-term effort to delineate the functional contribution of canonical and non-canonical nucleotide metabolite mRNA 5¢ end caps and their removal in the control of RNA stability and gene expression. Regulation of RNA turnover is a critical step in the modulation of gene expression and minor alterations in mRNA stability can have profound consequences and may manifest as clinical phenotypes. A key component controlling the fate of eukaryotic mRNA is the 5¢-end cap. Eukaryotic caps are generally thought to possess a canonical N7 methyl guanosine (m7G) cap at their 5¢-end to promote their stability and translation. Removal of the m7G cap (decapping) is exquisitely regulated and renders the RNA translationally silent and subject to rapid decay and gene silencing. Moreover, a recent exciting paradigm shift emerged with the demonstration that eukaryotic RNAs can also carry noncanonical 5´end nucleotide metabolite caps, initially of nicotinamide adenine diphosphate (NAD) and subsequently flavin adenine dinucleotide (FAD) and Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Such caps provide a potential link between RNA metabolism and cellular metabolism. However, there is a major gap in our understanding of these novel caps and their physiological function as well as their unambiguous identification. Thus, a detailed mechanistic understanding of the individual novel nucleotide metabolite capped RNAs and their functional consequence on cellular energetics and gene expression will have broad implications for cells in both normal and disease states.

项目摘要 拟议的研究集中于我们为描述功能贡献的长期努力 规范和非统治的核苷酸代谢物mRNA 5¢末端盖及其在 控制RNA稳定性和基因表达。 RNA更新的调节是关键的步骤 基因表达的调节和mRNA稳定性的较小改变可以具有深刻的 后果并可能表现为临床表型。控制命运的关键组成部分 真核mRNA是5¢ - 末端盖。通常认为真核帽具有规范 N7甲基鸟嘌呤（M7G）盖在其5¢端盖，以促进其稳定性和翻译。消除 M7G盖（decappapping）的完全调节，并使RNA翻译沉默，并且 受到快速衰减和基因沉默。此外，最近出现了令人兴奋的范式转变 通过证明真核RNA也可以携带非宗教核5'END核苷酸 代谢物帽，最初是烟酰胺腺嘌呤二磷酸（NAD），然后是黄素 腺嘌呤二核苷酸（FAD）和尿苷二磷酸N-乙酰葡萄糖胺（UDP-GLCNAC）。这样的 CAPS提供了RNA代谢与细胞代谢之间的潜在联系。但是，那里 是我们对这些新颖帽子及其身体功能的理解的主要差距 作为他们明确的识别。那，对个人的详细机械理解 新型的核苷酸代谢物限制了RNA及其对细胞能的功能后果 基因表达对正常和疾病状态的细胞都有广泛的影响。