Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

The following is intended to complement the contents of a different type of review (611) of this topic. In contrast to triplet tRNA anticodon: codon interaction, the hybrid lengths central to DNA dependent RNA polymerases, and RNA dependent DNA polymerases, are much longer and of course without the counterpart of an adjacent tRNA (Thermus thermophilus RNAP hybrid oscilates between 9 and 10 bp during forward and backward translocation on DNA). Post initiation region slippage by bacterial RNA polymerase was initially detected in vitro (612) and shown to occur with high efficiency in vivo with a run of 9 As or Ts (613) . Productive utilization of slippage at 9 Ts in the Thermus thermophilus dnaX gene yields a heterogeneous population of mRNAs with 1 or multiple additional As in a diminishing proportion such that standard translation yields about 50% of the product being full length (323). Without context features, slippage is not detectable at TTTTTCC-CCC (T5C5). However, an IS element from Roseiflexus bacteria utilizes context-dependent slippage at this sequence to generate transcripts lacking a C residue within the corresponding U5C4 mRNA. Standard translation of these mR-NAs yields its transposase (99) . The enabling context feature is formation of a nascent RNA stem loop structure from the inverted repeat sequence, GCGGGCgcaaGCC-CGC 5 adjacent to the U5C5/U5C4 motif (99) (Figure 18 ).