The Interface of RNA Biology and the Translation Machinery

RNA exists as a complex, modified and dynamic nucleic acid in cells capable of directing gene expression through an array of properties. Epitranscriptomic modifications and secondary structure guide fine tuning of splicing, RNA stability and translation of transcripts by the protein synthesis machinery. The interplay between RNA and the translation machinery constitutes a crucial role in gene expression in crucial processes such as development and hematopoiesis. A deeper knowledge of how elements of RNA modifications and structure impact translation of specific transcripts opens windows into hematopoietic decisions of differentiation versus stemness.

Our lab seeks to define out epitranscriptomic changes impact specificity in protein synthesis across an array of contexts including pediatric bone marrow failure and oncogenesis predisposition.

Dissecting Nascent Gene Expression

Gene expression is the culmination of linked processes including transcription, RNA processing and ultimately translation and modification of proteins. Deciphering the relative contribution of each of these on the final protein abundance has been difficult to address until recent advances. Prior, mRNA concentrations had been used as proxy for, and thus the main determinant, of protein abundance. However, transcript abundance only partially predicts respective protein abundance. When considering immediate, nascent gene expression as in response to a new stimulus, translational control governs rapid regulation of cellular protein levels in many eukaryotic mRNAs and translation rates may dwarf that of transcription by as much as 70-fold. Therefore, understanding how cells receive cues and quickly respond with nascent gene expression programs implores analysis at the proteomic level.

We employ cutting edge techniques to probe rapid gene expression responses to delve deeper into how models of hematopoiesis sense and adapt to pharmacologic blockade, shifting cytokines and metabolic fluctuations.