Mechanisms of mRNA frame maintenance and its subversion during translation of the genetic code

Important viral and cellular gene products are regulated by stop codon readthrough and mRNA frameshifting, processes whereby the ribosome detours from the reading frame defined by three nucleotide codons after initiation of translation. In the last few years, rapid progress has been made in mechanistically characterizing both processes and also revealing that trans-acting factors play important regulatory roles in frameshifting. Here, we review recent biophysical studies that bring new molecular insights to stop codon readthrough and frameshifting. Lastly, we consider whether there may be common mechanistic themes in -1 and +1 frameshifting based on recent X-ray crystal structures of +1 frameshift-prone tRNAs bound to the ribosome.