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Rapid Isolation of the Mitoribosome from HEK Cells
Published on: October 4, 2018
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Elongational stalling activates mitoribosome-associated quality control.
Nirupa Desai1, Hanting Yang1, Viswanathan Chandrasekaran1
1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Science (New York, N.Y.)
|November 27, 2020
Summary
Researchers discovered a quality control pathway in human mitochondrial ribosomes (mitoribosomes) that rescues stalled protein synthesis. Key proteins eject nascent chains and tRNA, ensuring proper function of oxidative phosphorylation complexes.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The human mitochondrial ribosome (mitoribosome) is crucial for synthesizing 13 essential oxidative phosphorylation (OXPHOS) subunits.
- Mitoribosome function is vital for cellular energy production.
Purpose of the Study:
- To discover and characterize a quality control pathway for stalled mitoribosomes.
- To elucidate the structural mechanisms of ribosome rescue.
Main Methods:
- Cryo-electron microscopy (cryo-EM) at 3.1- to 4.4-angstrom resolution.
- Biochemical analysis of protein-RNA and protein-protein interactions.
Main Results:
- Structures of mitoribosomal large subunits trapped during ribosome rescue were determined.
- Identified C12orf65 (mtRF-R) and C6orf203 (MTRES1) as key factors in ejecting nascent chains and peptidyl-tRNA.
- Observed recruitment of mitoribosome biogenesis factors to quality control intermediates.
- Provided structures of elongating mitoribosomes with elongation factors and Oxa1L.
Conclusions:
- A novel mitoribosome-associated quality control pathway rescues stalled translation during elongation.
- mtRF-R and MTRES1 play critical roles in mitoribosome rescue.
- Mitoribosome biogenesis factors have additional roles in quality control.
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