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

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.