Analysis of functional genetic variants in RNA processing and expression

RNA加工和表达中的功能性遗传变异分析

基本信息

批准号：
10240961
负责人：
Xinshu Grace Xiao
金额：
$ 53.13万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-01 至 2023-01-31
项目状态：
已结题

项目摘要

Project Summary The goal of this project is to functionally annotate genetic variants in post-transcriptional regulation of RNA expression, which extends and complements the current focus of ENCODE data analysis. Recently, tremendous success has been achieved in constructing a catalog of genetic variants in disease genomes or across population. The next great challenge is to identify causal variants and elucidate their potential function in biological and disease processes. To this end, research efforts have been directed to studying variants located in protein-coding, promoter, and splice site regions due to their apparent impacts on gene expression. However, many of the newly identified disease-associated variants reside in other non-coding regions, such as introns, that may confer regulatory function to the related gene. The mechanisms of these variants have been hard to decipher. It is expected that many of them may function at the post-transcriptional level, thus affecting mRNA expression. In human, a myriad of processes mediate RNA expression at the post-transcriptional stage, such as splicing, editing, polyadenylation and mRNA decay. Post-transcriptional regulation is extremely versatile, yet closely regulated, affecting most human genes. Despite the importance, how to accurately identify functional genetic variants in these processes remains a key question in the field. To address this question, the large collection of ENCODE expression and protein-binding data represent an invaluable resource. We will develop novel methodologies to make full use of the ENCODE and other publicly available data sets, complemented by further bioinformatic prediction and experimental validations. This work will allow a previously unattained level of understanding of genetic variants in post-transcriptional regulation of RNA expression and provide new means to tackle the imperative task of functional annotations of genetic variants.

项目摘要该项目的目的是在转录后的功能上注释遗传变异 RNA表达的调节，它扩展并补充了当前的编码重点数据分析。最近，在构建一个目录中取得了巨大成功疾病基因组或跨种群中的遗传变异。下一个巨大的挑战是识别因果变异并阐明其在生物和疾病中的潜在功能过程。为此，研究工作已针对研究位于蛋白质编码，启动子和剪接位点区域由于对基因的明显影响表达。但是，许多新确定的与疾病相关的变体都存在于其他可能赋予相关基因调节功能的非编码区域，例如内含子。这些变体的机制很难破译。预计他们中的许多人可能在转录后水平上起作用，从而影响mRNA表达。在人类中在转录后阶段（例如剪接）介导RNA的表达编辑，聚腺苷酸化和mRNA衰变。转录后法规非常通用，尚未受到密切调节，影响大多数人类基因。尽管很重要，但如何准确在这些过程中识别功能性遗传变异仍然是该领域的关键问题。到解决这个问题，大量编码表达和蛋白质结合数据代表宝贵的资源。我们将开发新颖的方法来充分利用编码和其他公开数据集，通过进一步的生物信息学补充预测和实验验证。这项工作将允许以前无名的水平了解RNA表达的转录后调节中遗传变异的理解提供新的手段来应对遗传变异功能注释的当务之急。