Spacer-length dependence of programmed -1 or -2 ribosomal frameshifting on a U(6)A heptamer supports a role for messenger RNA (mRNA) tension in frameshifting

Lin, Zhaoru; Gilbert, Robert J. C.; Brierley, Ian

The mRNA signal for À1 FS is composed of two elements, a slippery sequence with consensus X_XXY_ YYZ (underlines denote zero frame; X can be any base, Y is A or U, Z is not G in eukaryotic systems) where the ribosome changes frame, and a downstream stimulatory RNA structure, a stem-loop or pseudoknot (reviewed in 3, 4) . Appropriate spacing (typically 5-8 nt) between slippery sequence and stimulatory RNA is also required for optimal À1 FS efficiency (11) (12) (13) . There is considerable experimental support for the idea that 'tandem-slippage' of ribosome-bound peptidyl-and aminoacyl-tRNAs on the slippery sequence occurs upon encounter of the stimulatory RNA, with the tRNAs detaching from the zero frame *To whom correspondence should be addressed. Tel: [phone]; Fax: [phone]; Email: codons (XXY_YYZ) and re-pairing in the À1 frame (XXX_YYY) (6, 14) . What actually drives tRNA movement in frameshifting is uncertain. There is accumulating evidence to suggest involvement of an intrinsic unwinding activity of the ribosome (15) , with the stimulatory RNA exhibiting resistance to unwinding, perhaps by presenting an unusual topology. Failure to unwind the stimulatory RNA appropriately has been proposed to induce tension in the mRNA leading to uncoupling of the codon:anticodon complexes and realignment of the tRNAs in the À1 frame (16) (17) (18) (19) (20) (21) (22) (23) (24) (25) (26) (27) (28) (29) .