1-Methylguanosine in Place of Y Base at Position 37 in Phenylalanine tRNA Is Responsible for Its Shiftiness in Retroviral Ribosomal Frameshifting

AbstractMany mammalian retroviruses express their protease and polymerase by ribosomal frameshifting. It was originally proposed that a specialized shifty tRNA promotes the frameshift event. We previously observed that phenylalanine tRNAPhe 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 tRNAPhe contains 1-methylguanosine (m1G) in place of Y and that the m1G form from rabbit reticulocytes stimulates frameshifting more efficiently than its m1G-containing counterpart from mouse neuroblastoma cells. The latter tRNA contains unmodified C and G nucleosides at positions 32 and 34, respectively, while the former tRNA contains 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′ side of the anticodon render tRNAPhe shifty, but the modification status of the entire anticodon loop contributes to the degree of shiftiness. Possible biological consequences of these findings are discussed