Novel Assay System and Analysis Algorithm in Detecting RNA Editing Events and Linked Splicing Isoforms
Novel Assay System and Analysis Algorithm in Detecting RNA Editing Events and Linked Splicing Isoforms
批准号:
9184137
负责人:
Ke Hao
金额:
$17.4万
依托单位:
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:
2016-07-01 至 2018-06-30
关键词:
5&apos Untranslated RegionsAdenosineAlgorithmsAnimalsAutopsyBindingBinding SitesBiological AssayBiological SciencesBrainCandidate Disease GeneCodeCodon NucleotidesCommunitiesComplementary DNAComplexComputational algorithmDNA MethylationDetectionDevelopmentDiseaseEventFrequenciesFunctional disorderGene DosageGene ExpressionGenesGenomeGoalsGuanosineHaplotypesHeroin AbuseInosineIntronsLengthLinkMainstreamingMajor Depressive DisorderMediator of activation proteinMessenger RNAMethodsMicroRNAsMolecularMolecular BiologyNeurologicNucleotidesPerformancePhaseProcessProtein IsoformsProteinsProtocols documentationRNARNA EditingRNA SplicingReadingResearchResearch PersonnelRoleSamplingSeriesSerotonin Receptor 5-HT2CSignal TransductionSiteSpecimenStatistical Data InterpretationSubstance Use DisorderSystemSystems AnalysisTechnologyTestingTimeUntranslated RNAValidationVariantabstractingaccomplished suicideassay developmentbasecomputerized toolsdrug abusergene functionillicit drug usenervous system disordernovelnovel strategiessequencing platformserotonin receptorsingle moleculetooltranscriptomevector
中文摘要
摘要
英文摘要
Abstract
RNA editing is a process in which the genome-encoded information is altered in RNA. RNA editing is an
efficient way to increase RNA complexity, thereby fine-tuning both gene function and dosage. Adenosine to
Inosine (A-to-I) editing is the most common type of RNA editing known in animals. The cellular machinery
recognizes inosine as guanosine, so A-to-I editing of codons and splicing signals directly modifies protein-
coding gene function, whereas editing of microRNAs and their binding sites alter gene expression. The vast
majority of A-to-I editing, however, is detected in non-coding regions (e.g. Alu-repeats within introns and 3' or 5'
untranslated regions), strongly suggesting a still unknown regulatory role of this cellular mechanism.
Dysregulation of mRNA editing was implicated in several neurological diseases. In addition, we and other
groups showed that alterations in mRNA editing of one of the serotonin receptors (serotonin 2C receptor) is
associated with completed suicide, major depression and possibly substance use disorder (SUD). Currently,
short read Sanger or Illumina sequencing are the mainstream tools in RNA editing studies. However, these
tools cannot detect the “phase” of editing events; i.e., they cannot detect simultaneous editing events at two or
more sites which are situated further than 50-100bp from one another on the same mRNA molecule. In
addition, the current tools, which focus on a small region in the vicinity of a given editing site, do not allow us to
study RNA editing in the context of splicing. In the proposed project we aim to develop a state-of-the-art tool
that can be used by the entire scientific community. If we are successful, this tool will enable a simultaneous
detection and quantification of RNA editing and splicing isoforms in the brain hence allowing researchers to
study RNA editing in the context of splicing. Moreover, this tool will enable determination of the haplotypes of
mRNA molecules with multiple editing sites. We anticipate that this tool will have a great commercial potential
and will facilitate research on RNA editing as one of the molecular mechanisms that is implicated in SUD.
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