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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
Hungry codons promote frameshifting in human mitochondrial ribosomes.
Richard Temperley1, Ricarda Richter, Sven Dennerlein
1The Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Science (New York, N.Y.)
|January 16, 2010
Summary
Human mitochondria use a unique genetic code, recoding arginine codons (AGA, AGG) as stop signals. This study reveals these codons, with other elements, induce frameshifting in human mitochondrial ribosomes.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Mitochondria possess a non-universal genetic code, differing from the standard genetic code.
- Human mitochondria uniquely recode arginine codons (AGA, AGG) into stop signals, a rare phenomenon in mammals.
- This recoding presents a significant challenge in understanding mitochondrial gene expression.
Purpose of the Study:
- To investigate the mechanism behind the recoding of AGA and AGG codons in human mitochondria.
- To determine if a frameshift event is involved in the interpretation of these codons.
- To elucidate the role of specific codons and cis elements in mitochondrial ribosome frameshifting.
Main Methods:
- Utilized a sequence-specific endoribonuclease to probe mitochondrial translation.
- Analyzed the behavior of human mitochondrial ribosomes in response to specific RNA sequences.
- Investigated the influence of rare arginine codons and associated cis-acting elements on ribosome dynamics.
Main Results:
- Demonstrated that rare arginine codons (AGA, AGG) promote a -1 frameshift in human mitochondrial ribosomes.
- Showed that this frameshifting mechanism allows for the recognition of standard termination codons (UAA, UAG).
- Indicated that cis elements, in conjunction with the rare codons, are crucial for inducing frameshifting.
Conclusions:
- The recoding of arginine codons in human mitochondria is mediated by a programmed -1 frameshift event.
- This frameshifting mechanism is essential for generating functional mitochondrial proteins by resolving non-canonical stop signals.
- Findings provide novel insights into the complexities of mitochondrial genetic code and translation regulation.
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