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

Accurate maintenance of the translational reading frame is essential in the production of functional proteins and spontaneous frameshifting occurs rarely, with an estimated frequency (in Escherichia coli) of 3 Â 10 À3 -5Â 10 À5 per codon (1) . In some genes, however, mRNA elements are present that induce the ribosome to change reading frame at very high frequencies (reviewed in [2] [3] [4] . These sites of programmed ribosomal frameshifting direct ribosomes into an overlapping open reading frame (ORF), generating a fusion protein containing the products of both upstream and downstream ORFs. Most widespread are sites of programmed À1 ribosomal frameshifting (-1 FS) where the ribosome slips back one nucleotide (nt) in the 5 0 -direction on the mRNA. Frameshifting in eukaryotes was first described as the mechanism by which the Gag-Pol polyprotein of the retrovirus Rous sarcoma virus (RSV) is expressed from overlapping gag and pol ORFs (5,6) and related signals have since been documented in many other viruses, including the clinically important human immunodeficiency virus types 1 and 2 (7) (HIV-1, HIV-2), human T-cell lymphotrophic virus types 1 and 2 (8, 9) and the coronavirus responsible for severe acute respiratory syndrome (10) . Frameshifting has also been increasingly recognized in conventional cellular genes of both prokaryotes and eukaryotes as well as in other replicating elements, such as insertion sequences and transposons.