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Alternative pre-mRNA Splicing in Drosophila

果蝇中的选择性前 mRNA 剪接

基本信息

批准号：
8457021
负责人：
DONALD C RIO
金额：
$ 38.23万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
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：
2012-05-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8457021
关键词：
Address Affect Alternative Splicing Base Pairing Binding Binding Sites Biochemical Bioinformatics Biological Assay Cell Nucleus Cells ChIP-seq Data Defect Disease Drosophila genome Drosophila genus Elements Event Functional RNA Funding Gene Duplication Gene Expression Gene Mutation Genes Genetic Genome Genomics Grant Health Heterogeneous-Nuclear Ribonucleoprotein Group A-B Homologous Gene Human In Vitro Informatin Introns Investigation Lead Learning Link Malignant Neoplasms Methods MicroRNAs Modeling Mus Myotonic Dystrophy Organism Pathway interactions Pattern Phosphorus Process Property Protein Splicing Protein Structure Initiative Proteins Proteome Proteomics RNA RNA Binding RNA Interference RNA Processing RNA Splicing RNA-Binding Proteins RNA-Protein Interaction Recruitment Activity Regulation Regulatory Element Repression Repressor Proteins Research Role Site Small RNA Split Genes System Testing Testis Therapeutic Intervention Tissues Transcript Transcriptional Silencer Elements U1 Small Nuclear Ribonucleoprotein Work abstracting cell type genome-wide genome-wide analysis human disease in vivo insight mRNA Precursor novel paralogous gene protein protein interaction

项目摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY / ABSTRACT Alternative pre-mRNA splicing in Drosophila. D. Rio - PI Alternative pre-mRNA splicing is an important mechanism for regulating gene expression in metazoans. Indeed, RNA processing is a conduit through which genomic information is transferred to proteomic information. Because most eukaryotic genes are split and have the potential for alternative splicing, a dramatic increase in proteomic diversity among cells, tissues and organisms is a direct consequence of alternative splicing. In fact, it is now recognized that 30-40% of the known human and mouse disease gene mutations affect the splicing process. Thus, understanding how introns are recognized and how patterns of alternative splicing are set up may allow therapeutic intervention. Splicing silencers are a major type of RNA control element generating tissue- or cell type-specific splicing patterns in metazoans. Our previous work has focused on characterization of the tissue-specific Drosophila P element splicing silencer element. Recent work from our group has focused on tissue-specific regulation of alternative splicing and how the action of hnRNP proteins, PSI and the hnRNP A/B family proteins, hrp48, 40, 38 and 36 results in splicing silencer function. We wish to extend these studies to investigate the function of a Drosophila paralog of U2AF, called LS2, that functions as a splicing repressor. Building on previous R21 funding, we will continue investigations of the microRNA pathway protein, Ago-2, in alternative splicing pathways. Finally, using a variety of approaches, we want to identify and functionally characterize new cellular splicing silencers that are controlled by multiple splicing factors. One advantage this proposal has is the small genome size and well-annotated Drosophila genome that allows a comprehensive analysis of both alternative splicing patterns and the genome-wide distribution of RNA binding proteins. Because most eukaryotic genes are split and have the potential for alternative splicing, increased proteomic diversity among cells, tissues and organisms is a direct consequence of alternative splicing. Because the protein factors involved in controlling patterns of alternative splicing have homologs in humans and like humans Drosophila has extensive alternative splicing, results obtained in this system will have direct relevance and application to human health.

描述（由申请人提供）：