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 ribosomal frameshifting. It was originally proposed that a specialized shifty tRNA 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 stimulates frameshifting more efficiently than its m(1)G-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 tRNA(Phe) shifty, but the modification status of the entire anticodon loop contributes to the degree of shiftiness. Possible biological consequences of these findings are discussed.
Carlson
B A
BA
Section on the Molecular Biology of Selenium, National Cancer Institute, Bethesda, Maryland, 20892, USA.
Mushinski
J F
JF
Henderson
D W
DW
Kwon
S Y
SY
Crain
P F
PF
Lee
B J
BJ
Hatfield
D L
DL
D000818:Animals; D001483:Base Sequence; D018965:Frameshifting, Ribosomal; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D008099:Liver / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000737:chemistry; D009690:Nucleic Acid Conformation; D012360:RNA, Transfer, Phe / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000737:chemistry; D012190:Retroviridae / Q000235:genetics*
C116616:8-methylguanosine; D012360:RNA, Transfer, Phe; D006151:Guanosine; C012099:wye; D006147:Guanine