The role of the RNA regulon in the control of gene expression

RNA调节子在基因表达控制中的作用

• 批准号: BB/F02326X/2
• 负责人: Anne Willis
• 金额: $ 64.58万
• 依托单位: MRC Toxicology Unit
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF02326X%2F2
• 关键词: role; RNA; regulon; control; gene

Protein synthesis is the process by which the information in the genetic material in the cell, DNA, is converted via an intermediary substrate mRNA, into proteins. For proteins to be synthesised the mRNA must interact with a large complex called the ribosome which consists of RNAs and proteins. Ribosomes are able to decode the genetic information that is held in the mRNA and carry out the synthesis of the proteins. When mammalian cells are exposed to external agents that can damage the cell one of first things to happen is that protein synthesis is almost totally switched off. This is part of the cell's defensive mechanism since it allows the cell to repair the damage and recover from stress. However, whilst overall protein synthesis is decreased under these types of conditions, certain proteins still need to be made that allow the cell to recover from the damage. For example, we have shown that following treatment of cells with the type of UV-light that is found in sunlight, there is increased synthesis of proteins that are required to repair the damage that is caused to the DNA by this light. We have also found that under these conditions the cells use a different mechanism to synthesise proteins. However, data from other researchers have shown that under different conditions of cell stress e.g. when there is a reduced amount of oxygen present, different subsets of proteins are synthesised that are specific to the type of stress induced. This shows that there is coordinated regulation of protein synthesis following cell insult. The important question that needs to be addressed is how does this occur? Our results suggest that the mRNAs that are translated during cell stress contain important information in their non-coding regions (untranslated region UTR) that allows their recruitment to the ribosomes. In this proposal we aim analyse large amounts of data to identify the regions within the mRNAs that allow ribosome recruitment under different conditions of cell stress.

蛋白质合成是细胞中遗传物质DNA中的信息通过中间底物mRNA转化为蛋白质的过程。要合成蛋白质，信使核糖核酸必须与称为核糖体的大型复合体相互作用，核糖体由RNA和蛋白质组成。核糖体能够破译信使核糖核酸中的遗传信息，并进行蛋白质的合成。当哺乳动物细胞暴露在可能损害细胞的外部介质中时，首先发生的事情之一是蛋白质合成几乎完全关闭。这是细胞防御机制的一部分，因为它允许细胞修复损伤并从压力中恢复。然而，尽管在这些类型的条件下整体蛋白质合成减少，但仍需要某些蛋白质来使细胞从损伤中恢复。例如，我们已经证明，在用阳光中发现的那种紫外线处理细胞后，修复这种光对DNA造成的损伤所需的蛋白质合成增加。我们还发现，在这些条件下，细胞使用不同的机制来合成蛋白质。然而，来自其他研究人员的数据表明，在不同的细胞应激条件下，例如当氧气含量减少时，会合成不同亚组的蛋白质，这些蛋白质针对诱导的应激类型而异。这表明，在细胞损伤后，蛋白质合成存在协调调节。需要解决的重要问题是，这是如何发生的？我们的结果表明，在细胞应激过程中翻译的mRNAs在其非编码区(非翻译区UTR)包含重要信息，允许它们招募到核糖体。在这项建议中，我们的目的是分析大量数据，以确定在不同的细胞应激条件下，mRNAs中允许核糖体招募的区域。

项目成果

mTORC1-mediated translational elongation limits intestinal tumour initiation and growth.

• DOI: 10.1038/nature13896
• 发表时间: 2015-01-22
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Faller, William J.;Jackson, Thomas J.;Knight, John R. P.;Ridgway, Rachel A.;Jamieson, Thomas;Karim, Saadia A.;Jones, Carolyn;Radulescu, Sorina;Huels, David J.;Myant, Kevin B.;Dudek, Kate M.;Casey, Helen A.;Scopelliti, Alessandro;Cordero, Julia B.;Vidal, Marcos;Pende, Mario;Ryazanov, Alexey G.;Sonenberg, Nahum;Meyuhas, Oded;Hall, Michael N.;Bushell, Martin;Willis, Anne E.;Sansom, Owen J.
• 通讯作者: Sansom, Owen J.

The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration.

• DOI: 10.1093/nar/gkq294
• 发表时间: 2010-09
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Burrows C;Abd Latip N;Lam SJ;Carpenter L;Sawicka K;Tzolovsky G;Gabra H;Bushell M;Glover DM;Willis AE;Blagden SP
• 通讯作者: Blagden SP

The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

• DOI: 10.1371/journal.ppat.1004061
• 发表时间: 2014-04
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Hall BS;Hill K;McKenna M;Ogbechi J;High S;Willis AE;Simmonds RE
• 通讯作者: Simmonds RE

Trans-acting translational regulatory RNA binding proteins.

• DOI: 10.1002/wrna.1465
• 发表时间: 2018-05
• 期刊: Wiley interdisciplinary reviews. RNA
• 作者: Harvey RF;Smith TS;Mulroney T;Queiroz RML;Pizzinga M;Dezi V;Villenueva E;Ramakrishna M;Lilley KS;Willis AE
• 通讯作者: Willis AE

Temporal Regulation of Distinct Internal Ribosome Entry Sites of the Dicistroviridae Cricket Paralysis Virus.

• DOI: 10.3390/v8010025
• 发表时间: 2016-01-19
• 期刊: Viruses
• 作者: Khong A;Bonderoff JM;Spriggs RV;Tammpere E;Kerr CH;Jackson TJ;Willis AE;Jan E
• 通讯作者: Jan E