Non-coding RNA structure change in Chronic Obstructive Pulmonary Disease
慢性阻塞性肺疾病中非编码RNA结构的变化
基本信息
- 批准号:10743413
- 负责人:
- 金额:$ 70.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-01-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:3&apos Untranslated Regions3-Dimensional5&apos Untranslated RegionsAdenosineAdoptedAdultAffectAllelesAllyAlternative SplicingAreaBase PairingBinding ProteinsBiologicalBiological AssayBloodCandidate Disease GeneCationsCell LineCellsChargeChemicalsChemistryChronic Obstructive Pulmonary DiseaseCodeCollectionComplexCoupledDataDevelopmentDiseaseDistalEnvironmental Risk FactorEtiologyEventExhibitsExonsGene ExpressionGene Expression RegulationGenesGeneticGenetic DiseasesGenetic TranscriptionGenomeHumanIntronsLuciferasesLungLung diseasesMapsMeasuresMediatingMessenger RNAMutationOligonucleotidesOpen Reading FramesPatientsPlayPoly APolyadenylationPopulationPositioning AttributePost-Transcriptional RegulationProtein IsoformsProteinsQuantitative Trait LociRNARNA ProbesRNA SequencesRNA SplicingRNA-targeting therapyReporterResearchRibosomesRoleSamplingSingle Nucleotide PolymorphismSingle Nucleotide Polymorphism MapSiteSmokerSmokingStructureTechnologyTissuesTranscriptTranslationsUnited StatesUntranslated RNAUntranslated RegionsWorkalpha 1-Antitrypsinclinically relevantdesigndisorder riskgenome wide association studyinfancymRNA PrecursormRNA StabilitymRNA Translationnew technologynovelprogramsprotein expressionresponsesmall moleculetechnological innovationtherapeutic RNAthree-dimensional modelingtranscriptometranscriptome sequencingtranscriptomicstranslation assaytranslational impactvaping
项目摘要
SUMMARY
Chronic obstructive pulmonary disease (COPD) is a complex genetic disease associated with over 160 genes
coupled with numerous environmental factors. In most cases, the single-nucleotide polymorphisms (SNPs) most
strongly associated with COPD do not alter the protein coding sequence of genes but instead map to non-coding,
but often transcribed, regions of the genome, including UTRs and introns. Our collaborative work to date has
focused on how 5' and 3' UTR RNA structures are affected by SNPs and has revealed that many sequence
changes modulate RNA structures and alter translation of COPD-associated genes. Understanding of the
interrelationships between RNA structure and gene expression is in its infancy, has primarily focused on the
based-paired secondary structure of exons, and has been severely limited by our inability to fully explore RNA
structure in cells. We have developed three novel chemistry-based RNA structure probing strategies that allow
us to (i) investigate precursor mRNA structure in cells, (ii) identify regions in UTRs that likely adopt true higher-
order tertiary structure, and (iii) determine through-space contacts in RNAs and develop three-dimensional
models of their complex structures. These technologies open broad and long-term research areas into how
complex RNA structures modulate gene expression and how RNA structure is changed by SNPs associated with
disease. Another critical, allied development has been collection of extensive population-wide transcriptomic
(RNA-seq) data of COPD patient lung and blood tissues through consortia in which we participate. Based on
these transcriptomic data and their analysis, we have characterized important changes in both splicing and
polyadenylation of COPD associated genes; both processing events have important consequences on gene
expression. Our program also leverages substantial exploratory work that shows that RNA structure in coding
sequences of genes associated with COPD modulates their translation. For this proposal, we are now in a unique
position to leverage novel technologies and transcriptomic analyses to interrogate how RNA structure regulates
mRNA translation of COPD-associated genes. We expect to identify RNA structures that comprise robust targets
for RNA therapeutics designed to alter post-transcriptional gene regulation of protein expression. This project
will ultimately reveal new principles for how RNA structure regulates protein translation and alternative splicing
and will identify RNA regulatory structures in the human transcriptome associated with COPD.
总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alain T Laederach其他文献
Alain T Laederach的其他文献
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{{ truncateString('Alain T Laederach', 18)}}的其他基金
Variant induced RNA structure change in human genetic disease
人类遗传病中变异诱导的RNA结构变化
- 批准号:
10166301 - 财政年份:2021
- 资助金额:
$ 70.28万 - 项目类别:
Variant induced RNA structure change in human genetic disease
人类遗传病中变异诱导的RNA结构变化
- 批准号:
10410412 - 财政年份:2021
- 资助金额:
$ 70.28万 - 项目类别:
Variant induced RNA structure change in human genetic disease
人类遗传病中变异诱导的RNA结构变化
- 批准号:
10620737 - 财政年份:2021
- 资助金额:
$ 70.28万 - 项目类别:
Predicting the causative SNPs in LD blocks by allele-specific structural analysis
通过等位基因特异性结构分析预测 LD 块中的致病 SNP
- 批准号:
8792744 - 财政年份:2015
- 资助金额:
$ 70.28万 - 项目类别:
Predicting the causative SNPs in LD blocks by allele-specific structural analysis
通过等位基因特异性结构分析预测 LD 块中的致病 SNP
- 批准号:
9272151 - 财政年份:2015
- 资助金额:
$ 70.28万 - 项目类别:
Non-coding RNA structure change in Chronic Obstructive Pulmonary Disease
慢性阻塞性肺疾病中非编码RNA结构的变化
- 批准号:
10159303 - 财政年份:2012
- 资助金额:
$ 70.28万 - 项目类别:
Non-coding RNA structure change in Chronic Obstructive Pulmonary Disease
慢性阻塞性肺疾病中非编码RNA结构的变化
- 批准号:
8218425 - 财政年份:2012
- 资助金额:
$ 70.28万 - 项目类别:
Non-coding RNA structure change in Chronic Obstructive Pulmonary Disease
慢性阻塞性肺疾病中非编码RNA结构的变化
- 批准号:
8403664 - 财政年份:2012
- 资助金额:
$ 70.28万 - 项目类别:
Structural and functional consequences of disease SNPs on the transcriptome
疾病 SNP 对转录组的结构和功能影响
- 批准号:
8842659 - 财政年份:2012
- 资助金额:
$ 70.28万 - 项目类别:
Structural and functional consequences of disease SNP's on the transcriptome
疾病 SNP 对转录组的结构和功能影响
- 批准号:
10017258 - 财政年份:2012
- 资助金额:
$ 70.28万 - 项目类别:
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