Arginine methylation of hnRNPUL1 regulates interaction with NBS1 and recruitment to sites of DNA damage

Scientific Reports
Gayathri GurunathanStéphane Richard

Abstract

Arginine methylation is a post-translational modification required for the maintenance of genomic integrity. Cells deficient in protein arginine methyltransferase 1 (PRMT1) have DNA damage signaling defects, defective checkpoint activation and extensive genomic instability. Herein we identify the DNA damage protein and RNA binding protein, hnRNPUL1, to be a substrate of PRMT1. We identify the dimethylation of R584, R618, R620, R645, and R656, as well as the monomethylation of R661 R685 and R690 within hnRNPUL1 in U2OS cells by mass spectrometry. Moreover, we define the arginines within the RGG/RG motifs as the site of methylation by PRMT1 both in vitro and in vivo. The arginines 612, 618, 620, 639, 645, 656 and 661 within the human hnRNPUL1 RGG/RG motifs were substituted with lysines to generate hnRNPUL1(RK). hnRNPUL1(RK) was hypomethylated and lacked the ability to interact with PRMT1, unlike wild type hnRNPUL1. Co-immunoprecipitation studies showed that hnRNPUL1(RK) had impaired ability to associate with the DNA damage protein NBS1. Moreover, hnRNPUL1(RK) was not recruited to sites of DNA damage, unlike wild type hnRNPUL1, in the presence of transcriptional inhibitors. These findings define a role for arginine methylation dur...Continue Reading

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Methods Mentioned

BETA
immunoprecipitations
transfection
electrophoresis
immunoprecipitation
co-immunoprecipitation

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