Nascent Peptide and Small Molecule Mediated Translation Regulation

The goal of this work was to investigate how the interplay of the nascent peptide with the small molecule cofactors modulates ribosome function and as a consequence regulate gene expression in a cell. To study this we used regulatory peptides preceding erythromycin resistance methyltransferase (erm) genes as the model nascent peptides and macrolide antibiotics as model small molecule cofactors. Our studies expanded the general understanding of the mechanisms of functional interactions between the nascent peptide and the ribosomal tunnel, provided new insights into mechanisms of action of NPET-targeting antibiotics, illuminated new aspects of regulation of the resistance mechanisms and provided novel venues for future use of the discovered principles for practical purposes. We believe that unraveling the molecular networks of modulation of ribosomal function by nascent peptides in combination with small molecule cofactors is critical for understanding the basic principles of the regulatory circuitry of the cell.