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Terminating human mitochondrial protein synthesis: a shift in our thinking

Robert N Lightowlers1, Zofia M A Chrzanowska-Lightowlers

  • 1Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.

RNA Biology
|May 12, 2010
PubMed

Insights

Human mitochondria translation termination is not unusual. AGA/AGG codons trigger -1 frameshifting, allowing standard stop codons and a single release factor to terminate all mitochondrial gene products.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Human mitochondria were thought to use four stop codons (UAA, UAG, AGA, AGG) for translation termination.
  • The reassignment of arginine codons (AGA/AGG) as stop codons presented a puzzle regarding termination factor recognition.

Purpose of the Study:

  • To investigate the mechanism of translation termination for AGA/AGG codons in human mitochondria.
  • To determine the factors involved in recognizing these non-universal stop codons.

Main Methods:

  • Analysis of mitochondrial translation termination mechanisms.
  • Investigation of ribosomal frameshifting events.
  • Assessment of mitochondrial release factor (mtRF1a) sufficiency.

Main Results:

  • Human mitochondria do not utilize AGA/AGG as direct stop codons.
  • Absence of a cognate release factor or tRNA for AGA/AGG triggers -1 ribosomal frameshifting.
  • This frameshift repositions a standard UAG stop codon in the ribosomal A-site.
  • The universal stop codons UAA and UAG are sufficient for human mitochondrial translation termination.
  • A single mitochondrial release factor, mtRF1a, is sufficient to terminate all 13 encoded mitochondrial genes.

Conclusions:

  • Human mitochondrial translation termination relies on a conserved mechanism involving ribosomal frameshifting, not novel stop codons.
  • The mitochondrial genetic code employs a simplified termination system utilizing only UAA and UAG, recognized by mtRF1a.
  • This finding resolves the previous conundrum of AGA/AGG codon usage in human mitochondrial translation.

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