HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome

Mouzakis, Kathryn D.; Lang, Andrew L.; Vander Meulen, Kirk A.; Easterday, Preston D.; Butcher, Samuel E.

Prokaryotic ribosomes use two active mechanisms during translation to unwind RNA (49) . In the first mechanism, the ribosomal helicase activity raises the free energy of an encountered base pair by +0.9 kcal/mol (49) . This destabilizes the base pair, which can then be opened by the mechanical force generated by translocation. If the base pair is resistant to this force, tension may be created which is sensed at the codon-anticodon base pairs (31, 32, 43, 49, 51) . Because G-C pairs require more force for unwinding (49) , the tension sensed in the decoding center would be proportional to the local RNA stability (51) . The mechanical tension may either cause the tRNAs to slip 1 nt in the 5 0 -direction (5, 31, 32, 36, 49) or, alternatively, cause the ribosome to translocate incompletely by 2 nt instead of 3 nt (37), which would also result in a À1 frameshift.