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Research

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Our broad research interests focus on posttranscriptional gene control mechanisms. Questions pertaining to regulation of mRNA translation and decay, fascinate us as a group. We are specifically interested in understanding the mechanisms underlying mRNA fate decisions. We are intrigued by 'How does a cell decide to translate, store or degrade an mRNA at a given time?'. This question is relevant because mRNA fate decisions at the level of translation/decay play a critical role in various cellular processes as well as in diseases such as Cancer and Neurodegenerative Disorders. We apply a combination of biochemical, genetic, cell biological and genomic approaches to address our research questions. Yeast (S. cerevisiae) is our favorite model organism, however we also use mammalian cell culture system for addressing certain questions.

We are excited to address the following questions

1. How do low complexity sequences in proteins affect mRNA fate?

Low complexity sequences are characterized by repeats of amino acids of variable length. Some examples of such sequences are repeats of QN, RGG, SR, proline, glutamine, etc. We are interested in focussing on the role of RGG-repeat containing sequences in RNA-binding proteins. These proteins play a key role in several RNA metabolic processes. We focus on the role of these proteins in movement of mRNAs in and out of translation and decay steps. Interestingly, RGG-repeats (motifs) are sites of arginine methylation as well. We also focus on the role of arginine methylation in regulating RGG-repeat mediated mRNA fate decisions.
 

2. How do RNA granules (mRNP condensates) disassemble? 

RNA granules are conserved membrane-less RNA-protein complexes. The granules are also referred to as mRNP condensates and play a critical role in determining the functional status of mRNA in the cell. P-bodies and stress granules are well-characterized forms of RNA granules. The assembly mechanisms of RNA granules are well characterized. However we are focussing on disassembly of these granules which remains poorly understood. A strong motivation for understanding disassembly mechanisms is provided by observations pertaining to several neurodegenerative disorders such as ALS and FTLD. The patients of these diseases indicate accumulation of disassembly defective proteins aggregates that often contain key RNA-binding proteins and colocalize with RNA granules. 
 

3. Why and how do RNA processes in the nucleus and the cytoplasm crosstalk?

Mature mRNAs are exported from the nucleus to the cytoplasm in complex with predominantly nuclear shuttling RNA-binding proteins. We hypothesize a role of these shuttling proteins in regulating mRNA fate in the cytoplasm. Such a role is likely to act as a conduit for their role in nucleus to co-ordinate different steps of gene expression spanning from nucleus to the cytoplasm. On the other hand we are also excited to address possible nuclear role of predominantly cytoplasmic RNA-binding proteins. We hypothesize these proteins to travel to the nucleus in response to physiological cues such as genotoxic stress to modulate gene expression. The details underlying such cross-talk mechanisms fascinate us.
 

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