Carlson B A, Mushinski J F, Henderson D W, Kwon S Y, Crain P F, Lee B J, Hatfield D L
Section on the Molecular Biology of Selenium, National Cancer Institute, Bethesda, Maryland, 20892, USA.
Virology. 2001 Jan 5;279(1):130-5. doi: 10.1006/viro.2000.0692.
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.
许多哺乳动物逆转录病毒通过核糖体移码来表达其蛋白酶和聚合酶。最初有人提出,一种特殊的易移位tRNA会促进移码事件。我们之前观察到,在其反密码子3'侧缺乏高度修饰的怀丁苷(Y)碱基的苯丙氨酸tRNA(Phe)会刺激移码,这表明这种tRNA是易移位的。我们现在报告,易移位的tRNA(Phe)含有1-甲基鸟苷(m(1)G)来取代Y,并且来自兔网织红细胞的m(1)G形式比来自小鼠神经母细胞瘤细胞的含m(1)G对应物更有效地刺激移码。后一种tRNA在第32和34位分别含有未修饰的C和G核苷,而前一种tRNA在这些位置含有类似的2'-O-甲基化核苷。数据表明,不仅反密码子3'侧高度修饰碱基的缺失使tRNA(Phe)具有易移位性,而且整个反密码子环的修饰状态也有助于易移位程度。讨论了这些发现可能的生物学后果。