1-methylguanosine in place of Y base at position 37 in phenylalanine tRNA is responsible for its shiftiness in retroviral ribosomal frameshifting

Many mammalian retroviruses express their protease and polymerase by riboso mal frameshifting. It was originally proposed that a specialized shifty tRN A promotes the frameshift event. We previously observed that phenylalanine tRNA(Phe) lacking the highly modified wybutoxosine (Y) base on the 3' side of its anticodon stimulated frameshifting, demonstrating that this tRNA is shifty. We now report the shifty tRNA(Phe) contains 1-methylguanosine (m(1) G) in place of Y and that the m(1)G form from rabbit reticulocytes stimulat es frameshifting more efficiently than its m(1)G-containing counterpart fro m mouse neuroblastoma cells. The latter tRNA contains unmodified C and G nu cleosides at positions 32 and 34, respectively, while the former tRNA conta ins the analogous 2'-O-methylated nucleosides at these positions. The data suggest that not only does the loss of a highly modified base from the 3' s ide of the anticodon render tRNA(Phe) shifty, but the modification status o f the entire anticodon loop contributes to the degree of shiftiness. Possib le biological consequences of these findings are discussed. (C) 2001 Academ ic Press.