New insights into messenger RNA regulation in a baker’s yeast model


17 Jan 2017

New insights into messenger RNA regulation in a baker’s yeast model

 

New insights into messenger RNA regulation in a baker’s yeast model 

Posttranslational regulation of posttranscriptional gene control 

Dr Purusharth Rajyaguru, Intermediate Fellow

Indian Institute of Science, Bangalore

Synthesis of proteins is key for maintaining optimal status of a cell. The step involved in conversion of RNA to protein (translation) is highly regulated to control protein output in response to physiological status of cell. Our work identifies role of a posttranslational modification in regulating translation. Posttranslational modifications are chemical changes occurring on specific protein sequences. We have focused on arginine methylation (addition of methyl group to arginine amino acid) of a protein Scd6 that acts as a negative effector of translation (translation repressor). We have used baker’s yeast (Saccharomyces cerevisiae) as our model organism owing to a) the extreme ease of working with it and b) conservation of fundamental biological processes with humans. 

We observed that Scd6 gets arginine methylated and Hmt1 (the predominant methyltransferases in yeast) is required for its methylation. Characterization of the arginine methylation defective (AMD) mutant of Scd6 indicated that this modification is important for its repression activity. Specifically, the Scd6 AMD mutant fails to induce formation of RNA granules (markers of translation repression process).  Upon probing the molecular mechanism, we have learnt that methylated Scd6 is able to interact with Eukaryotic Translation Initiation Factor 4 Gamma 1 (eIF4G1) better than unmethylated Scd6. It has been observed earlier that Scd6 represses translation by targeting eIF4G1. Whether methylation directly improves binding of Scd6 to eIF4G1 remains to be explored.

This work helps us understand the contribution of arginine methylation to the fundamental process of mRNA fate determination. Since proteins with sequence and functional similarity (ortholog) to Scd6 are present in all higher organisms (including humans), we think that the finding reported by us might well be conserved in higher organisms. Further experiments will be required to test this idea. We are currently exploring if arginine methylation affects other translation repressors in similar manner. Our long-term goal is to understand the mechanistic basis of mRNA movements in and out of translation.

 

Figure description: Arginine methylation of Scd6 by Hmt1 augments its repression activity by promoting its interaction with eIF4G1.

Arginine methylation promotes translation repression activity of eIF4G-binding protein, Scd6. Gopalakrishna Poornima, Shanaya Shah, Venkadasubramanian Vignesh, Roy Parker and Purusharth I. Rajyaguru