Research Projects

Eukaryotic precursor messenger RNAs (pre-mRNAs) undergo processing at the 3'-untranslated region (UTR) through cleavage and polyadenylation. The regulation of cleavage events in gene expression is less explored, with a global analysis showing a heterogeneity where multiple cleavage events occur downstream of a PA-signal. This heterogeneity is thought to be random and is not well studied. Preliminary studies show a primary cleavage site with the highest occurrence of cleavage compared to other subsidiary sites. An inverse relationship between the number of cleavage sites and gene expression involved in oxidative stress response and myocyte hypertrophy is observed. The cleavage reaction is driven by the activity of the poly(A) polymerase in the cleavage and polyadenylation complex. Reduced cleavage heterogeneity and increased usage of the primary site induce gene expression during stress response and myocyte hypertrophy. The study aims to investigate the role of cleavage stuttering on gene expression, its implications in oxidative stress response and hypertrophy gene programs in the heart, and the regulation of cleavage heterogeneity by signaling pathways and phosphorylation of poly(A) polymerase star-PAP.