The growth and viability of an organism depends upon the fast and faithful decoding of that organisms genomic information into functional peptide sequences. High-accuracy protein synthesis helps to ensure that miscoded polypeptides are not produced, as errant polypeptides are prone to misfold and may have undesirable toxic consequences in the cell. The overall fidelity of protein synthesis appears to be limited by the action of the ribosome, which is the two-subunit macromolecular machine responsible for decoding and translating messenger RNAs (mRNAs) into protein in all organisms. During each cycle of translation elongation, the ribosome carefully selects the appropriate aminoacyl-tRNA (aa-tRNA) from a large com- peting pool. The selected aa-tRNA carries the amino acid that matches the mRNA codon currently in the ribosome’s decoding center, and is the only aa-tRNA permitted to enter the ribosome and incorporate a new amino acid onto the growing polypeptide chain. Similarly, during termination, the ribosome permits only protein release factors to enter the ribosome where they stimulate release of the nascent peptide.
Work in the Green lab is centered on the ribosome, and can be roughly divided into four general project areas. The longest-standing research area concerns the interactions of eubacterial ribosomes and release factors. The goal of these projects is to understand the mechanism of action of release factors on the ribosome. A second research area involves biochemical and structure/function studies of the miRNA pathway, particularly the mechanism of action of the Argonaute proteins and their interacting factors. A third area of work in the lab is centered around regulation of eukaryotic translation, specifically in understanding the mechanism behind various mRNA quality control pathways, and the interactions of proteins therein as well as with the ribosome. The newest area of research in the lab extends our strengths in ribosome biochemistry to characterize the translation status of the cell using the ribosome profiling. We are using this technique to better understand the role of several factors involved in eukaryotic and eubacterial translation fidelity.