Research Summary

Understanding mRNA fate decisions: Role of arginine-methylation in functional transitions of RNA-protein complexes (mRNPs)

Messenger RNAs transition through different functional states during their lifetime in cytoplasm. They can get 1. Translated 2. Stored in a translationallyrepressed state 3. Decapped and degraded. Control of mRNA translation and decay plays a crucial role in variety of cellular processes such as development & differentiation, learning & memory, regeneration and ageing. mRNA translation control involves movement of mRNAs between a translationally active state and a ribosome-free repressed state (often stored in mRNP aggregates). I aim to understand the mechanistic basis of these transitions, which have remained poorly explored so far. I will be using yeast as a model system to apply genetic, biochemical, imaging and genomic approaches to understand the above biological problem.

During my postdoctoral work, I identified an important role for a subset of RGG-motif proteins in repressing translation. These proteins repress translation by binding conserved translation initiation factor eIF4G in RGG-motif dependent manner. RGG-motifs have been shown to be sites of arginine methylation in some RGG-motif containing proteins such as FUS (fused in sarcoma), FMRP and HuD. I am currently probing the role of arginine methylation in regulating global mRNA translation and decay by modulating the functions of eIF4G-binding RGG-motif proteins.