The Jensen laboratory’s long-term research interest is the study of post-transcriptional gene regulation in the vertebrate nervous system, and in particular, how the metabolism of pre-mRNA and mRNA are controlled in neurons.
The precise control of protein expression is absolutely critical in biology, and the key decisions about which genes are turned on or off at any one moment control the proper growth and maturation of an organism during development, and are responsible for the organism’s homeostasis and proper response to environmental changes as an adult. Many gene expression programs are highly complex and controlled by regulating transcription of individual genes.
However, transcription is just the start of the process to produce an active protein. In vertebrates pre-mRNAs almost always contain introns, which must be accurately excised. Capping and polyadenylation are also regulated processes, as is the export of the mature mRNA from the nucleus. Finally, protein factors bound to specific mRNAs in the cytoplasm can dictate whether that message is translated or not, the half-life of the mRNA, and also the localization of the mRNA to a specific sub-cellular destination for highly localized protein expression.
Evidence suggests that neurons are a cell type that relies heavily on mechanisms of post-transcriptional gene regulation. During development neurons become highly polarized, acquiring an axon which can elongate and find distant synaptic targets.
While much is known about how axon growth cones respond to various guidance cues, the mechanisms by which the axon is able to translate this guidance cue information into cytoskeletal changes which allow the growth cone to expand or collapse is largely unexplored.
Recently, several laboratories have demonstrated that both growth cone chemoreplusion and chemoattraction are processes that are absolutely dependent upon local protein synthesis. The functional corollary of this finding is that axon guidance requires mRNA localization and translational control of some subset of mRNAs in the growth cone. This phenomenon of spatial gene regulation within an individual cell is a central research interest of this laboratory.