Exploring the roles of arginine methylation and deimination of the multifunctional nuclear proteins PSF and p54nrb

探索多功能核蛋白 PSF 和 p54nrb 精氨酸甲基化和脱亚胺化的作用

• 批准号: BB/D011795/1
• 负责人: Mark Dickman
• 金额: $ 25.71万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD011795%2F1
• 关键词: Exploring; roles; arginine; methylation; deimination

Many proteins undergo chemical modifications that can alter a particular function of protein. A common modification for example includes phosphorylation. Arginine methylation is now emerging as a mainstream post translational modification of proteins, similar to protein phosphorylation. It has recently been shown that the methylation of arginines can be antagonised enzymatically and it is therefore dynamic in nature. This offers exciting prospects that arginine methylation, as a eukaryotic post translational modification, may mirror phosphorylation in its level of complexity. Many RNA binding proteins undergo arginine methylation as a post translational modification. The methylation of arginine residues is thought to structurally alter the protein and therefore perturb protein-protein or protein nucleic interactions. We have recently used novel enrichment procedures to purify a multi protein nuclear complex from mammalian nuclear cell extracts in which PSF (polypyrimidine tract-binding protein associated splicing factor) is bound to p54nrb/NonO (Non-POU-domain-containing, octamer-binding protein) and identified sites of arginine methylation on the protein PSF. It is proposed to characterise the sites of arginine methylation of the multi-functional nuclear proteins PSF and p54nrb and further explore the roles of such modifications. The characterisation of post translational modifications (arginine methylation and citrullination) and exploring the roles played by such modifications on the multifunctional nuclear protein complex is an ideal forum for a multi-disciplinary experimental programme, encompassing aspects of biophysical techniques in the analysis of biological systems. The research will be performed within the Systems Biology group in the Department of Chemical and Process Engineering at the University of Sheffield.

许多蛋白质经过化学修饰，可以改变蛋白质的特定功能。例如，常见的修饰包括磷酸化。与蛋白质磷酸化类似，精氨酸甲基化现在正成为蛋白质的主流翻译后修饰。最近已经表明，甲基化的甜菜碱可以拮抗酶，因此它是动态的性质。这提供了令人兴奋的前景，精氨酸甲基化，作为真核生物的翻译后修饰，可能反映其复杂性水平的磷酸化。许多RNA结合蛋白经历精氨酸甲基化作为翻译后修饰。精氨酸残基的甲基化被认为在结构上改变蛋白质，因此干扰蛋白质-蛋白质或蛋白质核相互作用。我们最近使用了新的富集程序，从哺乳动物核细胞提取物中纯化多蛋白质核复合物，其中PSF（polypyrimidine tract-binding protein associated splicing factor）与p54 nrb/NonO（Non-POU-domain-containing，octamer-binding protein）结合，并鉴定了蛋白质PSF上的精氨酸甲基化位点。本文拟对多功能核蛋白PSF和p54 nrb的精氨酸甲基化位点进行定位，并进一步探讨其作用。翻译后修饰（精氨酸甲基化和瓜氨酸）的表征和探索这种修饰对多功能核蛋白复合物的作用是多学科实验计划的理想论坛，包括生物物理技术在生物系统分析中的各个方面。这项研究将在谢菲尔德大学化学与过程工程系的系统生物学小组内进行。

项目成果

Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.

• DOI: 10.1093/brain/awu120
• 发表时间: 2014-07
• 期刊: Brain : a journal of neurology
• 作者: Cooper-Knock J;Walsh MJ;Higginbottom A;Robin Highley J;Dickman MJ;Edbauer D;Ince PG;Wharton SB;Wilson SA;Kirby J;Hautbergue GM;Shaw PJ
• 通讯作者: Shaw PJ

A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.

Burkholderia pseudomallei毒素抑制翻译因子EIF4A的解旋酶活性。

• DOI: 10.1126/science.1211915
• 发表时间: 2011-11-11
• 期刊: Science (New York, N.Y.)
• 作者: Cruz-Migoni A;Hautbergue GM;Artymiuk PJ;Baker PJ;Bokori-Brown M;Chang CT;Dickman MJ;Essex-Lopresti A;Harding SV;Mahadi NM;Marshall LE;Mobbs GW;Mohamed R;Nathan S;Ngugi SA;Ong C;Ooi WF;Partridge LJ;Phillips HL;Raih MF;Ruzheinikov S;Sarkar-Tyson M;Sedelnikova SE;Smither SJ;Tan P;Titball RW;Wilson SA;Rice DW
• 通讯作者: Rice DW

Arginine methylation of REF/ALY promotes efficient handover of mRNA to TAP/NXF1.

• DOI: 10.1093/nar/gkq033
• 发表时间: 2010-06
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Hung ML;Hautbergue GM;Snijders AP;Dickman MJ;Wilson SA
• 通讯作者: Wilson SA

Luzp4 defines a new mRNA export pathway in cancer cells.

• DOI: 10.1093/nar/gkv070
• 发表时间: 2015-02-27
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Viphakone N;Cumberbatch MG;Livingstone MJ;Heath PR;Dickman MJ;Catto JW;Wilson SA
• 通讯作者: Wilson SA