Talk on Saturday 08:45-09:00am submitted by Amin Espah Borujeni
Translation initiation is controlled by RNA folding kinetics via a ribosome drafting mechanism
Amin Espah Borujeni (Chemical Engineering, Penn State University), Howard M. Salis (Chemical Engineering and Biological Engineering, Penn State University)
RNA folding plays an important role in controlling protein synthesis as well as other cellular processes. Existing models have focused on how RNA folding energetics control translation initiation rate under equilibrium conditions, but have largely ignored the effects of RNA folding kinetics. We introduce a new mechanism, called Ribosome Drafting, that explains how the ribosome’s binding rate and the mRNA’s folding kinetics collectively control its translation initiation rate. During cycles of translation, Ribosome Drafting takes place whenever fast-binding ribosomes bind to mRNAs with slow-folding RNA structures, maintaining the mRNA in non-equilibrium states, with an acceleration of protein synthesis. By designing RNA structures with disparate folding kinetics, but equivalent folding energetics, we show that Ribosome Drafting increases protein synthesis rates by over 1000-fold. Overall, we characterized protein synthesis rates from 30 mRNA variants with rationally designed ribosome binding rates, folding kinetics, and folding energetics to validate a non-equilibrium Markov model of translation and to confirm the necessary conditions for Ribosome Drafting. Our computational design, non-equilibrium modeling, and systematic experiments demonstrate a versatile approach for studying how RNA folding kinetics control cellular processes.
Keywords: Biophysical Model, Ribosome Drafting, RNA Folding Kinetics