Mechanism of U12-dependent spliceosomal splicing
U12依赖性剪接体剪接机制
基本信息
- 批准号:7772276
- 负责人:
- 金额:$ 29.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-03-01 至 2011-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressBindingBiochemistryCatalysisCellsCollectionComplexConserved SequenceDataDiseaseDistantDouble-Stranded RNADrosophila genusElementsEnvironmentEukaryotaExcisionGene ExpressionGene Expression RegulationGenesGenomeGrowth and Development functionHela CellsHumanHybridsIn VitroIndiumIntronsInvestigationLengthLibrariesLifeLinkMammalian CellMessenger RNAMetalcaptaseMethodsMinorMutationNuclearOrthologous GenePlantsPlayProteinsRNARNA InterferenceRNA SplicingRNA-Binding ProteinsReactionRecruitment ActivityRelative (related person)ReporterRibonucleoproteinsRoleSamplingSignal TransductionSiteSmall Nuclear RNASmall Nuclear RibonucleoproteinsSpecificitySpliceosomesStructureSystemTechniquesTestingTranscriptTriad Acrylic ResinWorkanalogbasecomplement systemdesignhigh throughput screeningin vivoknock-downmRNA Precursormembermutantnovelpublic health relevanceresearch studyresponsestem
项目摘要
DESCRIPTION (provided by applicant): The removal of introns from messenger RNA precursors by splicing is a mandatory step in the expression of most genes of higher eukaryotes. Previous work has defined a rare class of introns (U12-dependent introns) found in the genomes of most metazoan phyla. Members of this intron class are present in about 1 % of human genes including many with essential and/or disease-associated functions. Both the U12-dependent introns and the more abundant U2-dependent introns are spliced via a similar mechanism in large and complex ribonucleoprotein structures called spliceosomes. The two spliceosomes differ in their snRNA composition yet share significant similarities in the RNA-RNA interactions at the spliceosome core. These highly conserved sequences and interactions likely constitute the functional elements of the spliceosome. In addition, many but not all of the proteins involved in splicing appear to be shared between the two systems. A detailed understanding of the splicing signals and mechanism of this second splicing system is needed to understand the role of these introns in human gene expression and the biochemistry of splicing. This application proposes to examine the mechanism of splicing of this minor class of introns. First, RNA interference techniques will be used to screen for protein factors required for minor class splicing in Drosophila and mammalian cells. Second, experiments are proposed to investigate the specificity of spliceosome formation. RNA elements have been identified that control which spliceosomal RNAs interact with U12-dependent introns. The function of these elements and the factors they interact with will be investigated. Third, the critical functional features of minor class snRNAs will be identified including the exploration of relationships between these snRNAs and elements of self-splicing group II introns. Public health relevance: The regulated expression of genes is central to human growth, development, normal and pathological functioning and the response of the body to changes in the internal and external environment. An important point of gene regulation is the removal of introns from the primary transcripts of genes by RNA splicing. This proposal is designed to understand how the sites of splicing are correctly chosen and how the correct RNA fragments are linked together in the final mRNA products of human genes.
描述(由申请人提供):通过剪接从信使RNA前体中去除内含子是高等真核生物大多数基因表达的强制性步骤。以前的工作已经定义了一类罕见的内含子(U12依赖的内含子),发现在大多数后生动物门的基因组。该内含子类的成员存在于约1%的人类基因中,包括许多具有必需和/或疾病相关功能的基因。U12依赖性内含子和更丰富的U2依赖性内含子都通过类似的机制在称为剪接体的大型复杂核糖核蛋白结构中剪接。这两个剪接体的snRNA组成不同,但在剪接体核心的RNA-RNA相互作用中有显著的相似性。这些高度保守的序列和相互作用可能构成剪接体的功能元件。此外,许多但不是所有参与剪接的蛋白质似乎在两个系统之间共享。需要详细了解第二剪接系统的剪接信号和机制,以了解这些内含子在人类基因表达和剪接的生物化学中的作用。本申请提出研究这一小类内含子的剪接机制。首先,RNA干扰技术将用于筛选果蝇和哺乳动物细胞中小类剪接所需的蛋白质因子。其次,实验提出了调查的特异性剪接体形成。RNA元件已被确定为控制剪接体RNA与U12依赖性内含子相互作用。将研究这些要素的功能及其相互作用的因素。第三,次要类snRNAs的关键功能特征将被确定,包括这些snRNAs和自我剪接组II内含子的元素之间的关系的探索。公共卫生相关性:基因的调节表达是人类生长、发育、正常和病理功能以及身体对内外环境变化的反应的核心。基因调控的一个重要方面是通过RNA剪接从基因的初级转录本中去除内含子。该方案旨在了解剪接位点如何正确选择,以及正确的RNA片段如何在人类基因的最终mRNA产物中连接在一起。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
New connections between splicing and human disease.
- DOI:10.1016/j.tig.2012.01.001
- 发表时间:2012-04
- 期刊:
- 影响因子:11.4
- 作者:Padgett, Richard A.
- 通讯作者:Padgett, Richard A.
Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I.
- DOI:10.1126/science.1200587
- 发表时间:2011-04-08
- 期刊:
- 影响因子:0
- 作者:He H;Liyanarachchi S;Akagi K;Nagy R;Li J;Dietrich RC;Li W;Sebastian N;Wen B;Xin B;Singh J;Yan P;Alder H;Haan E;Wieczorek D;Albrecht B;Puffenberger E;Wang H;Westman JA;Padgett RA;Symer DE;de la Chapelle A
- 通讯作者:de la Chapelle A
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
RICHARD A PADGETT其他文献
RICHARD A PADGETT的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('RICHARD A PADGETT', 18)}}的其他基金
Functional consequences of mutations in spliceosomal small nuclear RNAs
剪接体小核RNA突变的功能后果
- 批准号:
10387440 - 财政年份:2019
- 资助金额:
$ 29.06万 - 项目类别:
Functional consequences of mutations in spliceosomal small nuclear RNAs
剪接体小核RNA突变的功能后果
- 批准号:
10221000 - 财政年份:2019
- 资助金额:
$ 29.06万 - 项目类别:
Mechanistic consequences of mutations in spliceosomal snRNAs
剪接体 snRNA 突变的机制后果
- 批准号:
8418565 - 财政年份:2012
- 资助金额:
$ 29.06万 - 项目类别:
Mechanistic consequences of mutations in spliceosomal snRNAs
剪接体 snRNA 突变的机制后果
- 批准号:
8976856 - 财政年份:2012
- 资助金额:
$ 29.06万 - 项目类别:
Mechanistic consequences of mutations in spliceosomal snRNAs
剪接体 snRNA 突变的机制后果
- 批准号:
8782489 - 财政年份:2012
- 资助金额:
$ 29.06万 - 项目类别:
Mechanistic consequences of mutations in spliceosomal snRNAs
剪接体 snRNA 突变的机制后果
- 批准号:
8595323 - 财政年份:2012
- 资助金额:
$ 29.06万 - 项目类别:
Transcriptional elongation and splicing in human genes in situ
人类基因的转录延伸和原位剪接
- 批准号:
8307820 - 财政年份:2010
- 资助金额:
$ 29.06万 - 项目类别:
Transcriptional elongation and splicing in human genes in situ
人类基因的转录延伸和原位剪接
- 批准号:
8050472 - 财政年份:2010
- 资助金额:
$ 29.06万 - 项目类别:
Transcriptional elongation and splicing in human genes in situ
人类基因的转录延伸和原位剪接
- 批准号:
8147002 - 财政年份:2010
- 资助金额:
$ 29.06万 - 项目类别:
Transcriptional elongation and splicing in human genes in situ
人类基因的转录延伸和原位剪接
- 批准号:
8509712 - 财政年份:2010
- 资助金额:
$ 29.06万 - 项目类别:
相似国自然基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:32170319
- 批准年份:2021
- 资助金额:58.00 万元
- 项目类别:面上项目
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
- 批准号:
- 批准年份:2021
- 资助金额:58 万元
- 项目类别:
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
- 批准号:31672538
- 批准年份:2016
- 资助金额:62.0 万元
- 项目类别:面上项目
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
- 批准号:31372080
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
P53 binding protein 1 调控乳腺癌进展转移及化疗敏感性的机制研究
- 批准号:81172529
- 批准年份:2011
- 资助金额:58.0 万元
- 项目类别:面上项目
DBP(Vitamin D Binding Protein)在多发性硬化中的作用和相关机制的蛋白质组学研究
- 批准号:81070952
- 批准年份:2010
- 资助金额:35.0 万元
- 项目类别:面上项目
研究EB1(End-Binding protein 1)的癌基因特性及作用机制
- 批准号:30672361
- 批准年份:2006
- 资助金额:24.0 万元
- 项目类别:面上项目
相似海外基金
Structural biochemistry studies on MAP kinase allosteric binding sites
MAP 激酶变构结合位点的结构生物化学研究
- 批准号:
8454542 - 财政年份:2011
- 资助金额:
$ 29.06万 - 项目类别:
Structural biochemistry studies on MAP kinase allosteric binding sites
MAP 激酶变构结合位点的结构生物化学研究
- 批准号:
8099975 - 财政年份:2011
- 资助金额:
$ 29.06万 - 项目类别:
Structural biochemistry studies on MAP kinase allosteric binding sites
MAP 激酶变构结合位点的结构生物化学研究
- 批准号:
8286268 - 财政年份:2011
- 资助金额:
$ 29.06万 - 项目类别:
BIOCHEMISTRY OF LEUKEMIA VIRUS CORE-BINDING FACTOR
白血病病毒核心结合因子的生物化学
- 批准号:
2099053 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别:
BIOCHEMISTRY OF LEUKEMIA VIRUS CORE-BINDING FACTOR
白血病病毒核心结合因子的生物化学
- 批准号:
3202487 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别:
Biochemistry of Leukemia Virus Core Binding Factor
白血病病毒核心结合因子的生物化学
- 批准号:
7161315 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别:
BIOCHEMISTRY OF LEUKEMIA VIRUS CORE-BINDING FACTOR
白血病病毒核心结合因子的生物化学
- 批准号:
2099054 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别:
Biochemistry of Leukemia Virus Core Binding Factor
白血病病毒核心结合因子的生物化学
- 批准号:
6829155 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别:
BIOCHEMISTRY OF LEUKEMIA VIRUS CORE BINDING FACTOR
白血病病毒核心结合因子的生物化学
- 批准号:
6475801 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别:
Biochemistry of Leukemia Virus Core Binding Factor
白血病病毒核心结合因子的生物化学
- 批准号:
8644851 - 财政年份:1993
- 资助金额:
$ 29.06万 - 项目类别: