For close to three decades, gene expression was thought to be predominantly regulated at the transcriptional level. However, the discovery of RNA silencing pathways and the realization that post-transcriptional control provides conserved mechanisms by which cells can rapidly change gene expression patterns have led to a renaissance in the field of post-transcriptional regulation. Post-transcriptional processes, such as mRNA processing, export, surveillance, silencing, and turnover, are interconnected by the use of common factors, forming a complex regulatory network that contributes to cell-type and organism-specific gene expression patterns.
To understand the molecular mechanisms that regulate gene expression at the post-transcriptional level, we have set a long-standing goal of using a combination of small-scale and functional genomic approaches. Our research aims to elucidate the intricate relationships between post-transcriptional processes and their impact on gene expression regulation, with the ultimate goal of developing novel therapeutic approaches for diseases caused by defects in post-transcriptional regulation.
The mRNA exists as a ribonucleoprotein particle (mRNP) throughout its entire lifespan, providing a platform for the binding of numerous proteins. Therefore, many RNA binding proteins play roles at multiple steps of the post-transcriptional pathway. Moreover, enzymes involved in general mRNA degradation and proteins involved in mRNA surveillance, RNA silencing, and translational repression, co-localize in mRNA processing bodies or P-bodies, discrete cytoplasmic foci, suggesting that these processes are interconnected.
Our research is focused on comprehensively mapping the effectors and interaction networks involved in post-transcriptional pathways, aiming to understand their connections with different cellular processes. We also aim to determine the contribution of post-transcriptional processes to global gene expression and identify endogenous targets. Our ultimate goal is to elucidate how the regulation of these targets leads to the complex phenotypes observed at the cellular and organismal levels when these pathways are perturbed.