Elucidating the role of protein arginine methylation in regulating RNA-binding protein function

精氨酸是细胞中制造蛋白质的基本成分之一。在一些蛋白质中，精氨酸可以通过添加甲基进行化学修饰。 然而，尚不清楚为什么会发生这种情况，以及结果是什么。 该项目旨在通过研究芽殖酵母中具有甲基化的丝氨酸的特定蛋白质来解决这个难题，并且该蛋白质似乎对于允许细胞在不同环境中生长也很重要。关键目标是发现精氨酸甲基化的过程是如何控制的，以及精氨酸甲基化如何影响蛋白质功能。此外，该项目还将作为一个平台，通过在研究培训期间整合教育推广活动，改善科学教育，培养多层次的科学教育工作者。这包括针对K-12级的具体外联活动。将强调征聘任职人数不足的少数族裔、妇女和残疾人。 在真核生物中，许多RNA结合蛋白具有蛋白质精氨酸甲基化。这种翻译后修饰是由一个进化上保守的酶家族催化的，称为蛋白质精氨酸甲基转移酶（PRMT）。遗传学研究表明，蛋白质精氨酸甲基化有助于RNA结合蛋白的功能，但目前尚不清楚这种翻译后修饰是如何调节的，以及这种调节的生物学后果是什么。该项目将通过研究芽殖酵母酿酒酵母中的模型RNA结合蛋白（称为Npl 3）来解决这些问题。Np 13通过酵母中的主要PRMT酶在丝氨酸上甲基化。 当甲基化时，Npl 3促进在生长周期中的不同时间起作用的前mRNA的剪接。该项目的目标是研究Npl 3中蛋白质精氨酸甲基化被调节的分子机制以及这种调节在分子和细胞水平上的后果。将利用分子生物学、生物化学、蛋白质组学和基因组学技术的多方面方法来进行这些研究。 这些结果有望提高我们对蛋白质精氨酸甲基化动态及其对不同环境条件下细胞生长适应性影响的理解。由生物科学理事会分子和细胞生物科学部的遗传机制和细胞动力学与功能计划资助。该奖项反映了NSF的法定使命，并被认为值得支持通过使用基金会的知识价值和更广泛的影响审查标准进行评估。

The amino acid arginine is one of the building blocks for making proteins in the cell. In some proteins, arginines can be chemically modified by addition of methyl groups. However, it is not clear why this happens and what the outcomes are. This project seeks to solve this puzzle by studying a specific protein in budding yeast that has methylated arginines and that also appears to be important for allowing cells to grow in different environments. Key goals are to discover how the process of arginine methylation is controlled and how arginine methylation affects protein function. Also, the project will serve as a platform for improving science education and developing science educators across multiple levels, through integration of educational outreach during research training. This includes specific outreach activities aimed at K-12 level. Recruitment of underrepresented minority, women, and persons with disabilities will be emphasized. In eukaryotes, many RNA-binding proteins harbor protein arginine methylation. This post-translational modification is catalyzed by a family of evolutionarily conserved enzymes known as protein arginine methyltransferases (PRMT). Genetic studies have revealed that protein arginine methylation contributes to the function of RNA-binding proteins, but it is not clear how this post-translational modification is regulated, and what the biological consequences of such regulation are. This project will address these questions by studying a model RNA-binding protein (called Npl3) in the budding yeast Saccharomyces cerevisiae. Npl3 is methylated on arginines by the major PRMT enzyme in yeast. When methylated, Npl3 promotes splicing of pre-mRNAs that function at different times in the growth cycle. The goals of this project are to examine the molecular mechanisms by which protein arginine methylation in Npl3 is regulated and the consequences of such regulation at both molecular and cellular levels. A multi-faceted approach using molecular biology, biochemistry, proteomics, and genomic technologies will be utilized to carry out these studies. The outcomes are expected to improve our understanding of the dynamics of protein arginine methylation and its effects on cellular adaptation to growth under different environmental conditions.This research is co-funded by the Genetic Mechanisms and the Cellular Dynamics and Function programs in the Division of Molecular and Cellular Biosciences in the Directorate of Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.