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MicroRNA-mediated regulation of viral replication

MicroRNA介导的病毒复制调节

基本信息

批准号：
BB/F02360X/1
负责人：
Catherine Jopling
金额：
$ 105.57万
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF02360X%2F1
关键词：
MicroRNA mediated regulation viral replication

项目摘要

Genes are long sections of DNA that are copied into long molecules of a similar substance, RNA. These messenger RNAs are interpreted by machines known as ribosomes to make proteins, which carry out the functions in our cells. Recently, it was found that some genes are copied to make very short sequences of RNA, known as microRNAs. MicroRNAs are not used to make protein themselves, but instead bind to messenger RNA molecules that have a matching sequence for the microRNA. This binding leads to a reduction in the amount of protein made from that messenger RNA, and so is important in controlling the levels of particular proteins present in a cell, and therefore the behaviour of the cell. The hepatitis C virus (HCV) genome is composed of a long strand of RNA, which enters liver cells where it is used as a template to make HCV proteins. These make more copies of the HCV RNA, a process known as viral replication. I recently found that miR-122, a microRNA that is only found in the liver, binds to a site in HCV RNA. This binding is needed for viral replication to occur. This positive effect on viral replication is very different to the negative effects on protein synthesis that miRNAs normally promote. Interestingly, if the miR-122 binding site from HCV is moved to a different place in a different gene, it acts to repress protein synthesis. The aim of this research is to understand how a microRNA can mediate two such different processes. As the location of the binding site is important for its function, versions of HCV will be made with sites in different locations and tested to see what the requirements for the site are. Proteins are known to be important for microRNAs to function, so proteins that bind to miR-122 while it interacts with HCV RNA will be detected. These will be compared to the proteins used by microRNAs to repress protein synthesis. Finally, experiments will be carried out to detect when in the HCV replication cycle miR-122 interacts. Together, these experiments will help to explain how miR-122 is able to regulate HCV replication. This research will be carried out in the RNA biology group in the new Centre for Biomolecular Sciences at the University of Nottingham. Researchers in the group work on several different aspects of RNA, and are based in state-of-the-art new laboratories with all the necessary facilities for RNA research.

基因是DNA的长片段，它们被复制成类似物质RNA的长分子。这些信使RNA被称为核糖体的机器解释为蛋白质，蛋白质在我们的细胞中执行功能。最近，人们发现，一些基因被复制，使非常短的RNA序列，称为microRNA。microRNA本身不用于制造蛋白质，而是与具有与microRNA匹配序列的信使RNA分子结合。这种结合导致由信使RNA产生的蛋白质的量减少，因此在控制细胞中存在的特定蛋白质的水平以及细胞的行为方面很重要。丙型肝炎病毒（HCV）基因组由一条长链RNA组成，它进入肝细胞，在那里它被用作制造HCV蛋白的模板。这些使更多的拷贝的HCV RNA，一个过程被称为病毒复制。我最近发现，miR-122，一种仅在肝脏中发现的microRNA，与HCV RNA中的一个位点结合。这种结合是病毒复制所必需的。这种对病毒复制的积极影响与miRNA通常促进的对蛋白质合成的负面影响非常不同。有趣的是，如果来自HCV的miR-122结合位点被移动到不同基因的不同位置，它会抑制蛋白质合成。这项研究的目的是了解microRNA如何介导两个不同的过程。由于结合位点的位置对其功能很重要，因此将在不同位置制备不同版本的HCV，并进行测试，以了解对位点的要求。已知蛋白质对microRNA的功能很重要，因此将检测到与miR-122结合同时与HCV RNA相互作用的蛋白质。这些将与microRNA用于抑制蛋白质合成的蛋白质进行比较。最后，将进行实验以检测何时在HCV复制周期中miR-122相互作用。总之，这些实验将有助于解释miR-122如何能够调节HCV复制。这项研究将在诺丁汉大学新成立的生物分子科学中心的RNA生物学小组进行。该小组的研究人员致力于RNA的几个不同方面，并位于最先进的新实验室，拥有RNA研究的所有必要设施。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Eukaryotic translation initiation factor 4AII contributes to microRNA-122 regulation of hepatitis C virus replication.

DOI：
10.1093/nar/gky262
发表时间：
2018-07-06
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Ahmed CS;Winlow PL;Parsons AL;Jopling CL
通讯作者：
Jopling CL

The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122.

DOI：
10.1093/nar/gkt941
发表时间：
2014-01
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Roberts AP;Doidge R;Tarr AW;Jopling CL
通讯作者：
Jopling CL

Targeting viral infection by microRNA inhibition.

DOI：
10.1186/gb-2010-11-1-201
发表时间：
2010-01-26
期刊：
Genome biology
影响因子：
12.3
作者：
Roberts AP;Jopling CL
通讯作者：
Jopling CL

Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs.

DOI：
10.1038/nsmb.2982
发表时间：
2015-04
期刊：
NATURE STRUCTURAL & MOLECULAR BIOLOGY
影响因子：
16.8
作者：
Dhir, Ashish;Dhir, Somdutta;Proudfoot, Nick J.;Jopling, Catherine L.
通讯作者：
Jopling, Catherine L.

Hepatitis C virus infects the endothelial cells of the blood-brain barrier.

DOI：
10.1053/j.gastro.2011.11.028
发表时间：
2012-03
期刊：
Gastroenterology
影响因子：
29.4
作者：
Fletcher NF;Wilson GK;Murray J;Hu K;Lewis A;Reynolds GM;Stamataki Z;Meredith LW;Rowe IA;Luo G;Lopez-Ramirez MA;Baumert TF;Weksler B;Couraud PO;Kim KS;Romero IA;Jopling C;Morgello S;Balfe P;McKeating JA
通讯作者：
McKeating JA