The splicing factor SF3b1 is a master regulator of the innate immune response to Mycobacterium tuberculosis
The splicing factor SF3b1 is a master regulator of the innate immune response to Mycobacterium tuberculosis
批准号:
9206482
负责人:
Robert Owen Watson
金额:
$18.56万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-02-01 至 2019-01-31
关键词:
AffectAllelesAnti-Bacterial AgentsBacteriaBacterial GenesCatalysisCellsChromatinComplexCytoplasmDataData SetDevelopmentELF3 geneEventExhibitsGene ExpressionGenesGenetic TranscriptionHealthHourHumanImmuneInfectionInflammation MediatorsInflammatoryInnate Immune ResponseKnowledgeLightMeasuresMessenger RNAMolecularMycobacterium tuberculosisPathogenesisPatternPhosphorylationPlatelet Factor 4PolyadenylationPopulationPositioning AttributePost-Transcriptional RegulationPost-Translational Protein ProcessingProductionProtein SplicingProteinsRNARNA ProcessingRNA SplicingRecruitment ActivityRegulationRegulonRoleSpliceosome Assembly PathwaySpliceosomesSystemTNF geneTestingTherapeuticTimeTranscriptTranscriptional ActivationTuberculosisVaccinesVirulenceWorkcombatcytokineexperimental studygenome-wideinsightmRNA Precursormacrophagepathogenpreferenceprogramsprotein expressionprotein protein interactionpublic health relevanceresponsevirtual
中文摘要
英文摘要
DESCRIPTION (provided by applicant): Mycobacterium tuberculosis, the causative agent of tuberculosis, has evolved a complex interface with the host macrophage in order to establish a replicative niche and promote infection. Upon infection, Mtb induces changes to host gene expression in order to down-regulate pro-inflammatory cytokines. Past work has provided overwhelming evidence that changes to host gene expression that occur in the hours immediately following infection are critical for Mtb to establish infection. However, very little i known about how gene expression changes are regulated at the level of mRNA processing and maturation. Our new work indicates that post-transcriptional control of gene expression is important during the response to Mtb and that pre- mRNA splicing is a major regulatory checkpoint during infection. The studies proposed here are intended to fill a critical void in our understanding of post-transcriptional control of the innate immune gene expression program and will shed light on how important human health pathogens like Mtb can manipulate host RNA processing in order to create a favorable niche. The information generated in these studies will contribute to the development of targeted vaccines and host-directed therapeutics aimed at modulating pre-mRNA splicing to enhance anti-bacterial and/or short circuit pro-bacterial gene expression programs.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.jmb.2016.04.030
发表时间:
2016-08
期刊:
Journal of molecular biology
影响因子:
5.6
作者:
[K. Patrick;S. Bell;R. Watson]
通讯作者:
K. Patrick;S. Bell;R. Watson
TRIM proteins polarize DNA sensing outcomes during the innate immune response to Mycobacterium tuberculosis
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批准号:9158187
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项目类别:
-
资助金额:$37.13万
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财政年份:2016
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负责人:Robert Owen Watson
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依托单位:
TRIM proteins polarize DNA sensing outcomes during the innate immune response to Mycobacterium tuberculosis
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批准号:9766070
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项目类别:
-
资助金额:$37.13万
-
财政年份:2016
-
负责人:Robert Owen Watson
-
依托单位:
海外基金