January 11 , 2007

Dynamics of Translation: The Role of Fluctuations in tRNA Selection by the Ribosome

Tae-Hee Lee

In vivo protein synthesis, or translation, is a vital cellular process to produce enzymes in the cell. To synthesize protein with the correct sequence dictated by mRNA, the ribosome selects the correct tRNA with an unusually high accuracy (~0.01% error probability). We monitored individual working ribosome during the initial selection of tRNA in real-time through single molecule FRET to study the origin of such a high translation fidelity. We observe that a slight difference in the interaction energy between the ribosome and tRNA yields a slight difference in the center position of tRNA fluctuating at the codon-recognition state, the very beginning stage of translation. This slight difference in the center position of tRNA can result in an exponential difference in the probability of tRNA reaching a long distance from its center position (i.e. probability of rare events falling on the tail of a Gaussian distribution can be exponentially different with a slight difference in the center position of the distribution). As results, we observe that the correct tRNA reaches the docking position in the ribosome more frequently and more accurately than does an incorrect one. Only after tRNA reaching the docking position, the system can proceed to next step. Therefore, tRNA fluctuations effectively amplify a slight difference in the interaction energy between the ribosome and tRNA, thereby yielding high translation fidelity.