A CHARACTERISTIC BENT CONFORMATION OF RNA PSEUDOKNOTS PROMOTES -1 FRAMESHIFTING DURING TRANSLATION OF RETROVIRAL RNA

The structures of four different RNA pseudoknots that provide one of t he signals required for ribosomal frameshifting in mouse mammary tumor virus have been determined by NMR. The RNA pseudoknots have similar s equences and assume similar secondary structures, but show significant ly different frameshifting efficiencies. The three-dimensional structu res of one frameshifting and one non-frameshifting RNA pseudoknot had been determined previously by our group. Here we determine the structu res of two new RNA pseudoknots, and relate the structures of all four pseudoknots to their frameshifting abilities. The two efficient frames hifting pseudoknots adopt characteristic bent conformations with stem 1 bending towards the major groove of stem 2. In contrast, the two poo r frameshifting pseudoknots have structures very different from each o ther and from the efficient frameshifters. One has linear, coaxially s tacked stems, the other has stems twisted and bent, but in the opposit e direction to the efficient frameshifters. Changes in loop size that favor bending (shorter loops) increase frameshifting efficiency; longe r loops that allow linear arrangement of the stems decrease frameshift ing. Frameshifting pseudoknots in feline immunodeficiency virus and si mian retrovirus have different loop sequences, but the sequences at th eir stem junctions imply the same bent conformation as in the mouse ma mmary tumor viral RNA. The requirement for a precise pseudoknot confor mation for efficient frameshifting strongly implies that a specific in teraction occurs between the viral RNA pseudoknot and the host protein -synthesizing machinery. (C) 1996 Academic Press Limited