Translation Initiation is Controlled by RNA Folding Kinetics via a Ribosome Drafting Mechanism

• DOI: 10.1021/jacs.6b01453
• Publication Date: 2016-05-20T10:05:21Z
• Authors: Amin Espah Borujeni; Howard M Salis
• Keywords: Folding (DSP implementation); Ribosomal binding site

RNA folding plays an important role in controlling protein synthesis as well other cellular processes. Existing models have focused on how energetics control translation initiation rate under equilibrium conditions but largely ignored the effects of nonequilibrium folding. We introduce a new mechanism, called "ribosome drafting", that explains mRNA's kinetics and ribosome's binding collectively its rate. During cycles translation, ribosome drafting emerges whenever successive ribosomes bind to mRNA faster than can refold, maintaining it state with acceleration synthesis. Using computational design, time-correlated single photon counting, expression measurements, we demonstrate slow-folding fast-folding structures equivalent vary rates by 1000-fold. determine necessary for characterizing mRNAs rationally designed rates, kinetics, energetics, confirming predictions Markov model translation. Our results widespread implications, illustrating competitive assembly shape gene machinery's sequence–structure–function relationship inside cells.