Translating ribosomes maintain reading frame with extreme accuracy. However,
certain RNA sequences program the ribosome to alter reading frame efficiently
to allow for the expression of alternative translational products. Sites
which cause the ribosome to shift frames, termed programmed frameshift sites,
occur in organisms from bacteria to higher eukaryotes. Mechanistically the
frameshift events are very diverse. Ribosomes may shift frames one base
in the leftward, or -1, direction, one base in the rightward, or +1, direction,
and can even shift over dozens of nucleotides in the rightward direction,
an event termed a translational hop. By studying the sequence requirements
of such sites, the primary sequence of the peptides produced, and the effect
of site-specific mutations researchers have defined the rules of programmed
frameshifting at a large number of sites of all three types. Though the
detailed mechanisms differ, the sites all conform to a general pattern.
Programmed frameshifting occurs when the ribosome transiently pauses during
elongation with a sequence in the decoding sites of the ribosome which predisposes
it to shift frames. In almost all cases, this predisposition results from
the ability of tRNAs to reposition themselves on cognate or near-cognate
codons in the new reading frame. However, this is not a universal requirement
since at least two programmed +1 frameshifts probably occur without tRNA
slippage. These events occur when the mRNA sequence of the frameshift site
manipulates the frame maintenance mechanism of the ribosome to increase
drastically the probability of frame disruption. They may therefore be used
as tools to probe this mechanism.