Overlapping cistrons in a family of ion channel genes

离子通道基因家族中的重叠顺反子

基本信息

批准号：
9132375
负责人：
Christopher Manuel Gomez
金额：
$ 42.01万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9132375
关键词：
Affinity Chromatography Autistic Disorder Behavioral Binding Binding Proteins Biology C-terminal Calcium Channel Cistrons Code Complex Connexins DNA Development Disease Electrophoretic Mobility Shift Assay Embryo Eukaryota Eukaryotic Initiation Factors Family Family member Gel Chromatography Gene Deletion Gene Expression Gene Family Gene Targeting Genes Genetic Glutamine Goals Health Hereditary Disease Heterozygote Human Genetics Immunohistochemistry In Vitro Incubated Internal Ribosome Entry Site Ion Channel Lead Longevity Luciferases Mass Spectrum Analysis Mediating Messenger RNA MicroRNAs Mutation Nature Nuclear Open Reading Frames P-Q type voltage-dependent calcium channel Pathogenesis Peptide Initiation Factors Pervasive Development Disorder Phenotype Play Precipitation Prevalence Property Proteins Purkinje Cells RNA RNA Binding RNA-Binding Proteins Regulation Reporter Role Schizophrenia Series Site Structure Trans-Activators Transcript Transgenic Mice Transgenic Organisms Translating Translations Type 6 Spinocerebellar Ataxia Vertebrates Western Blotting chromatin immunoprecipitation crosslink developmental disease genetic regulatory protein loss of function member multitask nerve supply nervous system disorder neurobehavioral disorder neuropsychiatric disorder notch protein novel pleiotropism polypeptide protein complex therapeutic target therapy development transcription factor transcriptome sequencing voltage

项目摘要

DESCRIPTION (provided by applicant): We have discovered that the CACNA1A gene, which encodes the P/Q type voltage gated calcium channel (VGCC) is bicistronic. The CACNA1A mRNA encodes both the a1A subunit and a second protein, a1ACT, a transcription factor, that is translated as a second open reading frame due to a cryptic internal ribosomal entry site (IRES). Simultaneous expression of two proteins in the same cellular mRNA, one of which is a transcription factor, may be a powerful strategy used by calcium channels and other cellular genes to coordinate expression of an ensemble of genes. To understand this new class of IRES and bicistronic genes we will: 1. Determine how the CACNA1A IRES is regulated by RNA-binding proteins and miRNAs; 2. Define the novel properties of bicistronic genes of the VGCC family. 3. Determine whether altered bicistronic gene expression leads to the complex phenotypes of VGCC disorders. This study will help us to understand the biology of bicistronic cellular genes in particular among other VGCCs, the nature of the IRES regulatory mechanisms and proteins they encode, and the possible role in the pathogenesis and treatment of complex human genetic disease.

描述（由适用提供）：我们发现编码P/Q类型电压门控钙通道（VGCC）的CACNA1A基因是双性恋的。 CACNA1A mRNA编码A1a亚基和第二个蛋白A1ACT，转录因子，由于密码学内部核糖体入口位点（IRES）而被翻译为第二个开放式阅读框。在同一细胞mRNA中同时表达了两种蛋白质，其中一种是转录因子，可能是钙通道和其他细胞基因使用的强大策略，用于协调基因集合的表达。为了了解这类新的IRES和双基因基因：1。确定Cacna1a IRES如何受RNA结合蛋白和miRNA的调节； 2。定义了VGCC家族的双质基因的新特性。 3。确定双质基因表达是否会导致VGCC疾病的复杂表型。这项研究将帮助我们了解双科斯特朗细胞基因的生物学，尤其是在其他VGCC中，它们所编码的IRES调节机制和蛋白质的性质以及在复杂人类遗传疾病的发病机理和治疗中的可能作用。