Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Kinetics of mRNA and tRNA Selection by the Ribosome

Ribosomes are molecular machines that synthesize proteins in the cell. The translation initiation efficiency of a given mRNA is determined by its translation initiation region (TIR). Recent kinetic data reveal the order of initiation factor binding to the 30S subunit and the adjustments within the complex in response to mRNA selection. At the stage of the 30S initiation complex formation mRNAs that lack extensive secondary structures at the AUG start codon bind to the ribosome proportionally to their cellular concentrations, while folded mRNAs form unproductive stand-by complexes that dissociate quickly. The conversion of the 30S initiation complex into the translating 70S ribosome constitutes another important mRNA control checkpoint for the stereochemical fitness of mRNA TIR, including the strength of the Shine-Dalgarno interaction, the length of the mRNA spacer from the Shine-Dalgarno sequence to the AUG codon, and the codon-anticodon interaction between the start codon and the initiator tRNA. The efficiency with which an mRNA enters the pool of translating ribosomes is controlled by the conformation of the 30S initiation complex, while the 50S subunit appears to be a sensor of the 30S initiation complex structure that provides the irreversibility of the reaction. Ribosomes take an active part in aminoacyl-tRNA selection by distinguishing correct and incorrect codon-anticodon pairs. Correct codon-anticodon complexes are recognized by a network of ribosome contacts that are specific for each position of the codon- anticodon duplex and involve A-minor RNA interactions. Recognition relies on the geometry of the codon-anticodon complexes and enables the ribosome to accept different cognate tRNAs with similar efficiency, irrespective of differences in sequence and structure. Single mismatches at any position of the codon-anticodon complex result in slower forward reactions and a uniformly 1000-fold faster dissociation of the tRNA from the ribosome, regardless of the thermodynamic stability of the respective codon-anticodon complexes or their docking partners at the decoding site.

Marina V. Rodnina

Dept. of Physical Biochemistry
Max Planck Institute
for Biophysical Chemistry
Am Fassberg 11
37077 Goettingen

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