Genomic Analysis of Nucleic Acid Transactions

核酸交易的基因组分析

• 批准号: 10797178
• 负责人: Brenton R. Graveley
• 金额: $ 24.54万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797178
• 关键词: Adaptive Immune System; Address; Alternative Splicing; Basic Science; CRISPR screen; Clustered Regularly Interspaced Short Palindromic Repeats; DNA; DNA Sequence; Development; Elements; Future; Gene Expression; Gene Proteins; Genes; Genetic Transcription; Genome; Genomics; Guide RNA; Health; Human; Immune system; Immunologic Memory; Invaded; Messenger RNA; Nucleic Acids; Organism; Plasmids; Process; Prokaryotic Cells; Proteins; Proteome; RNA Processing; RNA Splicing; RNA interference screen; RNA-Binding Proteins; Reporter; Role; System; Virus; Work; experimental study; genome editing; innovation; insight; mRNA Precursor; memory encoding; nanopore; nuclease; single-cell RNA sequencing; tool

Project Summary (as submitted in the original application) Most eukaryotic pre-mRNAs, especially in metazoans, are alternatively spliced to generate multiple mRNAs and proteins. Given the importance of alternative splicing in regulating gene expression and enhancing the diversity of the proteome, it is essential to understand the mechanisms of splicing and how alternative splicing is regulated. In this project, we will study the roles of RNA binding proteins in alternative splicing, with an emphasis on how RNA binding proteins auto- and cross-regulate the splicing their own and other RNA binding protein genes. This work will provide new insight into the mechanisms of RNA processing and how these proteins regulate one another to achieve homoestasis. Many prokaryotes encode CRISPR-Cas systems which are RNA-guided adaptive immune systems that protects prokaryotic organisms against invaders such as viruses and plasmids. Immune memories are encoded as short DNA sequences, called “spacers”, that match invader genomes and are stored as interspersed elements in an array of short repeats (the CRISPR array). The CRISPR arrays are transcribed and processed into guide RNAs which pair with Cas nucleases to recognize and degrade target nucleic acid (interference). New immune memories are formed during “adaptation” when fragments of invader DNA are acquired and integrated into CRISPR arrays for use in future targeting. While a tremendous amount is known about the targeting and degradation of invading nucleic acids, much less is known about the process of adaptation. We plan to further characterize the adaptation process in prokaryotic CRISPR-Cas systems. This work will also provide insight into the mechanisms of adaptation in the immune systems of prokaryotes. In addition to enhancing our understanding of the basic science of prokaryotic immune systems, there is tremendous potential that this work could lead to the development of new tools that can be used for genome editing applications. All of these projects will be addressed using the types of general approaches we have developed such as splicing reporters, single cell RNA-Seq, nanopore sequencing, RNAi or CRISPR screens, and computational genomics. We will also continue to develop additional innovative approaches to address these issues as needed or as opportunities arise due to technical advances in the field.

项目简介（在原始申请中提交）