Although it is unknown if pseudoknots stimulate À1 frameshifting and +1 frameshifting by different mechanisms, one notable difference is found in positioning of the downstream structure relative to the shift site. Naturally occurring pseudoknots or stem-loop stimulators of À1 frameshifting typically begin $6-9 nt downstream of the A-site codon of the shift site (18) , whereas +1 frameshift pseudoknots are located closer with only a 2-3 nt separation from the A-site codon (31) . Mutagenic studies have revealed that altering the size of the spacer affects frameshifting and, in general, reduces efficiency (27, 31, (42) (43) (44) .