Transcript-specific Translation: Mechanisms, Structures and Principles
Translation produces proteins that are the major determinants of cellular functions. In all organisms, translation is catalyzed in the ribosome, an extraordinary RNA-protein molecular machine in every living cell. Furthermore, 5’-untranslated regions (5’UTRs) of mRNA are essential for translation. The average length of 5’UTR sequences has increased over evolution, suggesting that their utilization contributes to the complexity of translational regulation and organism speciation. Professor Jin and her lab propose that structured 5’UTRs can facilitate translation initiation via sequential remodeling: the 5’UTR undergoes sequential conformational changes that are facilitated by RNA binding proteins and translational factors, which ultimately leads to recruitment of the ribosome for translation of the mRNA. Currently, the 5’UTR remodeling and activation remain structurally and mechanistically uncharacterized for eukaryotic mRNAs. To elucidate the molecular mechanisms, structures and principles important for this process, Professor Jin will determine the precise sequential events in the 5’UTR remodeling in transcript-specific translation and solve structures of biological complexes involved in this process using biochemistry and structural biology.
At present, initial data from Professor Jin’s lab suggests that unique interactions between the 5’UTR, associated proteins and the ribosome lead to formation of transcript-specific translation machinery important for cell physiology. Research in this area will not only open a new avenue of exploration in basic science, but also lead to medical innovations: uncovering disease-related mechanisms and providing therapies that directly target specialized translation.