Computational and Experimental Analysis of RNA structures in mRNA polyadenylation

mRNA 多腺苷酸化中 RNA 结构的计算和实验分析

• 批准号: 7895058
• 负责人: CAROL S LUTZ
• 金额: $ 23.4万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-22 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895058
• 关键词: Address; Biochemical; Bioinformatics; Biological; Biological Assay; Code; Computer Analysis; DNA Microarray Chip; Data; Data Set; Elements; Eukaryotic Cell; Event; Genes; Genome; Genomics; Goals; Human; Light; Location; Mass Spectrum Analysis; Messenger RNA; Metabolism; Mutation; Pattern; Play; Poly A; Poly(A) Tail; Polyadenylation; Polyadenylation Pathway; Process; Protein Isoforms; RNA; Regulation; Regulatory Element; Relative (related person); Role; Site; Structure; Testing; Tissues; Transcript; Translations; Variant; base; crosslink; experimental analysis; human disease; mRNA Stability; mammalian genome; protein complex; public health relevance

DESCRIPTION (provided by applicant): mRNA polyadenylation is a key processing event for almost all mRNAs in eukaryotic cells. It involves cleavage of maturing mRNAs at the 3' end and addition of a poly(A) tail. The poly(A) tail influences many aspects of mRNA metabolism, including mRNA stability, mRNA transport, and translation. Over half of all human genes have multiple polyadenylation sites, or poly(A) sites, leading to transcript variants containing distinct mRNA cis- regulatory elements and/or encoding protein isoforms. Alternative polyadenylation has been shown to be regulated in tissue- and condition-specific manners. A growing number of human diseases have been associated with altered polyadenylation activity. While the core elements for polyadenylation have been well characterized, little is known about the auxiliary elements that modulate polyadenylation activity. In particular, the role of RNA secondary structures in regulation of polyadenylation is completely unclear. The long term goal is to fully understand the mechanisms by which mRNA polyadenylation is regulated under different biological conditions. The specific aims of this study are 1) to systematically analyze different types of RNA structures associated with mammalian poly(A) sites by bioinformatics, and 2) to examine how RNA structures regulate mRNA polyadenylation by experimental assays. PUBLIC HEALTH RELEVANCE: mRNA polyadenylation is a key processing event for almost all mRNAs in eukaryotic cells. It involves cleavage of maturing mRNAs at the 3' end and addition of a poly(A) tail. The poly(A) tail influences many aspects of mRNA metabolism, including mRNA stability, mRNA transport, and translation. Over half of all human genes have multiple polyadenylation sites, or poly(A) sites, leading to transcript variants containing distinct mRNA cis- regulatory elements and/or encoding protein isoforms. Alternative polyadenylation has been shown to be regulated in tissue- and condition-specific manners. A growing number of human diseases have been associated with altered polyadenylation activity. While the core elements for polyadenylation have been well characterized, little is known about the auxiliary elements that modulate polyadenylation activity. In particular, the role of RNA secondary structures in regulation of polyadenylation is completely unclear. The long term goal is to fully understand the mechanisms by which mRNA polyadenylation is regulated under different biological conditions. The specific aims of this study are 1) to systematically analyze different types of RNA structures associated with mammalian poly(A) sites by bioinformatics, and 2) to examine how RNA structures regulate mRNA polyadenylation by experimental assays.

描述（由申请人提供）：mRNA聚腺苷酸化是真核细胞中几乎所有mRNA的关键处理事件。它涉及在3'端的成熟mRNA的切割，并添加聚（A）尾巴。 poly（a）尾部影响mRNA代谢的许多方面，包括mRNA稳定性，mRNA转运和翻译。所有人类基因的一半以上具有多个聚腺苷酸化位点或聚（a）位点，导致含有不同mRNA顺式调节元件和/或编码蛋白质同工型的转录物变体。替代的聚腺苷酸化已显示在组织和条件特异性的方式中受到调节。越来越多的人类疾病与多腺苷酸化活性改变有关。虽然多腺苷酸化的核心元素已经很好地表征了，但对调节聚腺苷酸化活性的辅助元件知之甚少。特别是，RNA二级结构在调节聚腺苷酸化调节中的作用尚不清楚。长期目标是充分了解在不同生物学条件下调节mRNA聚腺苷酸化的机制。这项研究的具体目的是1）系统地分析与哺乳动物聚（A）位点相关的不同类型的RNA结构，以及2）检查RNA结构如何通过实验测定法调节mRNA聚腺苷酸化。 公共卫生相关性：mRNA聚腺苷酸化是真核细胞中几乎所有mRNA的关键处理事件。它涉及在3'端的成熟mRNA的切割，并添加聚（A）尾巴。 poly（a）尾部影响mRNA代谢的许多方面，包括mRNA稳定性，mRNA转运和翻译。所有人类基因的一半以上具有多个聚腺苷酸化位点或聚（a）位点，导致含有不同mRNA顺式调节元件和/或编码蛋白质同工型的转录物变体。替代的聚腺苷酸化已显示在组织和条件特异性的方式中受到调节。越来越多的人类疾病与多腺苷酸化活性改变有关。虽然多腺苷酸化的核心元素已经很好地表征了，但对调节聚腺苷酸化活性的辅助元件知之甚少。特别是，RNA二级结构在调节聚腺苷酸化调节中的作用尚不清楚。长期目标是充分了解在不同生物学条件下调节mRNA聚腺苷酸化的机制。这项研究的具体目的是1）系统地分析与哺乳动物聚（A）位点相关的不同类型的RNA结构，以及2）检查RNA结构如何通过实验测定法调节mRNA聚腺苷酸化。

项目成果

6,12,18,24-Tetra-meth-oxy-4,10,16,22-tetra-kis-[(meth-oxy-carbon-yl)meth-oxy]-2,8,14,20-tetra-kis-(2-phenyl-eth-yl)resorcin[4]arene.

6,12,18,24-四甲氧基-4,10,16,22-四基-[(甲氧基-碳基)甲氧基]-2,8,14,20-四

• DOI: 10.1107/s1600536811051567
• 发表时间: 2012
• 期刊: Acta crystallographica. Section E, Structure reports online
• 作者: Pansuriya,PramodB;Friedrich,HolgerB;Maguire,GlennEM
• 通讯作者: Maguire,GlennEM

mRNA 3' end processing factors: a phylogenetic comparison.

• DOI: 10.1155/2012/876893
• 发表时间: 2012
• 期刊: Comparative and functional genomics
• 作者: Darmon SK;Lutz CS
• 通讯作者: Lutz CS