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

许多蛋白质都会经历化学修饰，从而改变蛋白质的特定功能。例如，一种常见的修饰包括磷酸化。精氨酸甲基化现已成为蛋白质翻译后修饰的一种主流，类似于蛋白质磷酸化。最近的研究表明，精氨酸的甲基化可以被酶拮抗，因此它在本质上是动态的。这为精氨酸甲基化提供了令人兴奋的前景，作为真核细胞的翻译后修饰，精氨酸甲基化可能反映出其复杂程度的磷酸化。作为翻译后修饰，许多RNA结合蛋白经历精氨酸甲基化。精氨酸残基的甲基化被认为会改变蛋白质的结构，从而扰乱蛋白质与蛋白质或蛋白质核之间的相互作用。我们最近使用新的富集法从哺乳动物核细胞提取物中纯化了一个多蛋白核复合体，其中PSF(多嘧啶结合蛋白相关剪接因子)与p54nrb/NONO(非POU结构域、八聚体结合蛋白)结合，并确定了PSF蛋白上的精氨酸甲基化位点。拟对多功能核蛋白PSF和p54nrb的精氨酸甲基化位点进行表征，并进一步探讨这种修饰的作用。确定翻译后修饰(精氨酸甲基化和瓜氨酸化)的特征并探讨这种修饰对多功能核蛋白复合体的作用是开展多学科实验方案的理想论坛，该方案涵盖了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和过程工程系的系统生物学小组内进行。

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.