Eukaryotic mRNAs are processed at the 3'-end in a two-step event: an endonucleolytic cleavage followed by addition of an adenosine tail by poly(A) polymerases (PAPs). Star-PAP and PAPa/? are the two primary PAPs in the nucleus involved in nuclear polyadenylation of mRNAs. While the two PAPs share similar processing factors, they regulate distinct niche of target mRNAs. Moreover, polyadenylation occurs alternately at multiple sites at the 3'-end in more than 70% of human genes (APA), encoding mRNA isoforms with different lengths that modulates gene expression. We are interested in defining the mechanism how different PAPs select target mRNAs and how these targets are exclusive for each PAP. We also study regulation of PAP specificity by post-translational modification, and how UTR specificity regulates alternative polyadenylation.

RNA binding motif protein 10 (RBM10) is a regulator of alternative splicing of apoptotic genes. We have identified a splicing independent function of RBM10 that regulates mRNA 3'-end processing of cardiac genes in hypertrophy in the heart and heart failure. We are interested in how RBM10 regulates cardiac hypertrophy and heart failure and signaling pathways involved in the regulation. We also study post-translational modifications such as phosphorylation in RBM10 in the regulation of cardiac gene expression in heart failure.

We have reported that majority of long non-coding RNAs (LncRNAs) are processed or regulated by Star-PAP. While most LncRNAs are polyadenylated, some have modified 3'-end. Interestingly, majority of the mRNAs/lncRNAs targeted by Star-PAP are involved cancer metastasis (CM) and metabolic diseases such as diabetes (DM). Preliminary observation suggest different processing pattern between mRNAs and lncRNAs under different disease conditions. Moreover differential Star-PAP level has been reported in CM and DM. We are interested to understand the difference in the mechanism of mRNA and lncRNA processing and how they are affected by signalling pathways under different diseases conditions.

Poly(A) tails are present not only on eukaryotic mRNA 3'-end but also on some of the bacterial mRNAs. While polyadenylation stabilizes mRNA in eukaryotes, presence of poly(A) tail marks degradation of bacterial mRNA. However, the exact mechanism for the functional difference is not known. Here, we aim to define the basic mechanism of mRNA stability between the two organisms and determine what links the two polyadenylation and stabilization pathways. Our transcriptomics data strongly suggests putative role of polyadenylation dependent mRNA stabilization in stress response, bacterial pathogenesis and nutrient starvation.

Lipotoxicity is a metabolic disorder that results from the over-activation of lipid signalling pathways leading to the accumulation of lipid intermediates in cells causing cellular distress and ultimately leads to Lipoapoptosis. Heart is one of majorly affected organ as it has a high caloric need for its functioning and performs extensive oxidation of fatty acids (FAs) to meet its requirements. Any disturbance in this fine-regulated network will lead to cardiac lipotoxicity resulting in cardiac dysfunction and heart failure. Preliminary studies in the laboratory have shown that most of the genes and lncRNAs involved in lipid metabolism are modulated by the 3?-end mRNA processing mediated through the Phosphoinositide (PI) signalling. We aim to understand the post-transcriptional regulation of lipid metabolizing genes affecting the lipid composition and the impact on PI signalling during the lipotoxic stress.