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

Abstract

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.

The ATPase Fap7 Tests the Ability to Carry Out Translocation-like Conformational Changes and Releases Dim1 during 40S Ribosome Maturation

“…Many clinically relevant antibiotics target the ribosome, and induce errors in all stages of the decoding process. Furthermore, while programmed ribosomal frameshift (PRF) is exploited by some viruses (and their host cells) to control the amount of their structural and enzymatic proteins available for viral particle assembly (Brierley, 1995; Caliskan et al, 2015; Dinman, 1995; Dunkle and Dunham, 2015), slippage of ribosomes in either direction (5’ (−1) or 3’ (+1)) will produce a truncated protein, or lead to mRNA degradation via nonsense-mediated decay (Belew and Dinman, 2015). …”

Conditional Switch between Frameshifting Regimes upon Translation of dnaX mRNA

“…Such programmed ribosome frameshifting (PRF) events are ubiquitous from viruses to mammals and operate at efficiencies from very low to as high as 80% (Tsuchihashi and Brown, 1992). PRF increases the coding capacity of genomes and regulates mRNA stability (Atkins and Gesteland, 2010;Baranov et al, 2002;Caliskan et al, 2015;Dinman, 2012;Dunkle and Dunham, 2015;Farabaugh, 1996b). In rare cases the ribosome can also shift by -2, -4, +2, +5, or +6 nucleotides (Fang et al, 2012;Lainé et al, 2008;Weiss et al, 1987;Yan et al, 2015).…”

Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions

“…Translation normally occurs sequentially in triplets of nucleotides (codons) with strict maintenance by the ribosome of fidelity and reading frame with error rates of 10 −3 to 10 −4 per codon (Dunkle and Dunham, 2015; Hansen et al, 2003; Jenner et al, 2010). There are cases when this well-established rule breaks down, where the genetic code can be recoded and altered in an mRNA-specific manner (called programmed).…”