Arginine methylation of DRBD18 differentially impacts its opposing effects on the trypanosome transcriptome

Arginine methylation is a posttranslational modification that impacts wide-ranging cellular functions, including transcription, mRNA splicing and translation. RNA binding proteins (RBPs) represent one of the largest classes of arginine methylated proteins in both mammals and the early diverging parasitic protozoan, Trypanosoma brucei. Here, we report the effects of arginine methylation on the functions of the essential and previously uncharacterized T. brucei RBP, DRBD18. RNAseq analysis shows that DRBD18 depletion causes extensive rearrangement of the T. brucei transcriptome, with increases and decreases in hundreds of mRNAs. DRBD18 contains three methylated arginines, and we used complementation of DRBD18 knockdown cells with methylmimic or hypomethylated DRBD18 to assess the functions of these methylmarks. Methylmimic and hypomethylated DRBD18 associate with different ribonucleoprotein complexes. These altered macromolecular interactions translate into differential impacts on the T. brucei transcriptome. Methylmimic DRBD18 preferentially stabilizes target RNAs, while hypomethylated DRBD18 is more efficient at destabilizing RNA. The protein arginine methyltransferase, TbPRMT1, interacts with DRBD18 and knockdown of TbPRMT1 recapitulates the effects of hypomethylated DRBD18 on mRNA levels. Together, these data support a model in which arginine methylation acts as a switch that regulates T. brucei gene expression.