My project aims at deciphering the mechanism of action of a critical Trypanosoma brucei RNA binding protein, DRBD18 and determine how arginine methylation impacts its interactions and functions.
Unlike most eukaryotes, Trypanosoma brucei primarily relies on post-transcriptional processes to regulate gene regulation. Our lab recently discovered that DRBD18, an abundant RNA binding protein is essential for growth of both bloodstream and procyclic form of T. brucei. When DRBD18 is depleted, transcriptome of T. brucei undergoes extensive re-arrangement. The methylation status of the three methylated arginines identified in DRBD18 drastically alters its function. Methylation of the identified residues promotes the mRNA stabilization activity of DRBD18 and hinders its destabilization activity. The methyltransferase TbPRMT1, interacts with and methylates DRBD18 in vivo. Depletion of TbPRMT1 alters the level of putative mRNA targets in agreement to the effects of hypomethylated DRBD18, suggesting that arginine methylation of DRBD18 acts as a switch that regulates transcriptome biology in T. brucei.
My work will define primary DRBD18 target mRNAs and establish their methylation-responsiveness on a genome wide level. Also, it will provide insight into the effector pathways that DRBD18 impacts.
Uncovering gene specific regulatory mechanism will enhance our knowledge towards the basic biology of T. brucei. The detailed understanding of essential parasite biology will continue to reveal unusual biology and, thereby contribute to the development of new drugs.
Jan Naseer Kaur, PhD
955 Main Street, Suite 5230
Phone: (716) 829-3307