Function of arginine methylation in post-transcriptional gene regulation

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Arginine methylation affects cellular processes through protein-protein interactions. Its role in the posttranscriptional control of gene expression is ill explored so far. The proposed project will deepen the understanding of the mechanisms by which protein modifications contribute to translational regulation. The focus is on the impact of arginine methylation on the function of the multidomain protein hnRNP K. hnRNP K is a specific regulator of reticulocyte 15-lipoxygenase (r15-LOX) mRNA translation, and an activator and substrate of c-Src kinase. HnRNP K is methylated in vitro and in vivo, but the methyltransferase (PRMT), substrate arginines and functional consequence(s) of the methylation are not known. I identified PRMT1 as the hnRNP K-methylating enzyme in vitro as well as in vivo and showed that endogenous hnRNP K and PRMT1 co-immunoprecipitate. In HeLa cells co-transfected with hnRNP K, c-Src and PRMT1, the hnRNP K/c-Src interaction and hnRNP K tyrosine phosphorylation were strongly reduced. This sup ports my hypothesis that hnRNP K methylation is a functionally important modification. Now I will identify the substrate arginines and generate tools to study whether methylation of hnRNP K affects its function in r15-LOX mRNA translation control and its cellular localization.