Terminating human mitochondrial protein synthesis: a shift in our thinking.
Until recently, human mitochondria were regarded as unusual as they appeared to employ four stop codons to terminate translation. In addition to the UAA/UAG of the universal genetic code, two arginine triplets (AGA/AGG) had been re-assigned as termination signals. This posed the conundrum of what factor was responsible for recognizing these triplets to promote translation termination? Recent data indicates that in fact no protein is required to recognize AGA/AGG. Indeed, it is the absence of any cognate factor, tRNA or polypeptide that is important. On encountering either of these 'hungry' codons at the end of an open reading frame, instead of requiring a novel or modified release factor, human mitoribosomes employ -1 frameshifting to reposition a standard UAG codon in the A-site, indicating that only the universal UAA and UAG are used as stop codons. This renders a single mitochondrial release factor, mtRF1a, previously shown to be capable of terminating 11 of the 13 open reading frames encoded by the mitochondrial genome, to be sufficient to release all nascent human mitochondrial gene products from the mitoribosome.
Lightowlers
Robert N
RN
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Chrzanowska-Lightowlers
Zofia M A
ZM
D000595:Amino Acid Sequence; D018388:Codon, Terminator / Q000378:metabolism; D003210:Concept Formation; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010443:Peptide Chain Termination, Translational / Q000235:genetics / Q000502:physiology*; D010454:Peptide Termination Factors / Q000378:metabolism / Q000502:physiology; D014176:Protein Biosynthesis / Q000235:genetics; D013850:Thinking
D018388:Codon, Terminator; D024101:Mitochondrial Proteins; D010454:Peptide Termination Factors