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MicroRNA buffering of gene duplications and aneuploidy

基因重复和非整倍性的 MicroRNA 缓冲

基本信息

批准号：
1791658
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1791658
关键词：
MicroRNA buffering gene duplications aneuploidy

项目摘要

Aneuploidy and large-scale chromosomal duplications are common characteristics of many cell lines, including those derived from cancers. Despite these large-scale genome changes, these cell lines remain viable. Cellular processes that buffer against the effects of gene duplication and deletion are therefore key to cell viability. MicroRNAs are short RNA molecules that modulate gene function through translational repression, and are frequently characterised as buffers for gene dosage. This project will use a combination of computational and genetic approaches to study the roles of microRNAs as buffers of gene and chromosome duplications. We will analyse available genomes of cell lines for common losses and duplications of protein-coding genes and microRNAs, and available transcriptomic data as a source of gene and microRNA expression data. We will ask the following questions: 1. Are common sets of protein-coding and microRNA genes duplicated or lost in diverse cell lines?2. Are genes that are duplicated or lost in cell lines more or less likely to be targeted by microRNAs?3. What is the effect of duplication of microRNA and/or target gene on their expression levels?We will manipulate the expression of both microRNAs and their target genes, simulating the effects of gene duplication, in cell lines derived from various animal systems, including cancer cell lines. A variety of assays will be used to assess the contribution of both microRNA and target genes to buffering gene duplication and aneuploidy. Understanding how microRNAs buffer the consequences of aneuploidy will provide key insights into cell viability, including in diseases such as cancer, and the consequences of gene duplication.

非整倍性和大规模染色体复制是许多细胞系的共同特征，包括源自癌症的那些。尽管这些大规模的基因组变化，这些细胞系仍然是可行的。因此，缓冲基因复制和缺失影响的细胞过程是细胞活力的关键。MicroRNA是通过翻译抑制调节基因功能的短RNA分子，并且经常被表征为基因剂量的缓冲剂。该项目将使用计算和遗传方法的组合来研究microRNA作为基因和染色体复制缓冲器的作用。我们将分析可用的细胞系基因组中蛋白质编码基因和microRNA的常见丢失和重复，以及可用的转录组数据作为基因和microRNA表达数据的来源。我们将提出以下问题：1。常见的蛋白质编码和microRNA基因组在不同的细胞系中是复制还是丢失？2.在细胞系中复制或丢失的基因是否更有可能被microRNA靶向？3. microRNA和/或靶基因的复制对其表达水平有什么影响？我们将操纵microRNA及其靶基因的表达，模拟基因复制的影响，在来自各种动物系统的细胞系中，包括癌细胞系。将使用各种测定来评估microRNA和靶基因两者对缓冲基因复制和非整倍性的贡献。了解microRNA如何缓冲非整倍性的后果将提供对细胞活力的关键见解，包括癌症等疾病以及基因复制的后果。