Imaging protein translation from micron to atomic scales

Translation is an evolutionarily conserved process in which the ribosome, mRNA and tRNA coordinately synthesize new proteins. Here, I focus on two emerging technologies for studying the complex dynamics of translation at scales ranging from nanometer to atomic resolution. Single particle tracking of mRNAs and nascent peptide using Halo dyes revealed where translation of secretory and membrane proteins occurs on ER. The findings uncovered a novel coordination between ER and lysosomes in the patterning and regulation of translation of secretory/membrane proteins involving local release of amino acids and other factors from lysosomes adjacent to ER. To study translation at the atomic scale, we employed High Resolution Template Matching (HRTM) to examine ribosomes at different stages of peptide elongation in cryo-EM images of intact human cells. Combining reconstructions across 41 native conformations, we obtained a high-resolution movie of ribosome dynamics revealing ligand movements during polypeptide chain elongation and spring-like intramolecular motion. Together, these new tools open-up a plethora of questions related to translation and its mechanism that can now be studied in intact cells at the nanometric/atomic level.