A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit

Pedro Rebelo-Guiomar, Simone Pellegrino, Kyle C. Dent, Aldema Sas-Chen, Leonor Miller-Fleming, Caterina Garone, Lindsey Van Haute, Jack F. Rogan, Adam Dinan, Andrew E. Firth, Byron Andrews, Alexander J. Whitworth, Schraga Schwartz, Alan J. Warren and Michal Minczuk ()
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Pedro Rebelo-Guiomar: University of Cambridge, Cambridge Biomedical Campus
Simone Pellegrino: University of Cambridge, Cambridge Biomedical Campus
Kyle C. Dent: University of Cambridge, Cambridge Biomedical Campus
Aldema Sas-Chen: Weizmann Institute of Science
Leonor Miller-Fleming: University of Cambridge, Cambridge Biomedical Campus
Caterina Garone: University of Cambridge, Cambridge Biomedical Campus
Lindsey Van Haute: University of Cambridge, Cambridge Biomedical Campus
Jack F. Rogan: STORM Therapeutics Limited, Babraham Research Campus
Adam Dinan: University of Cambridge
Andrew E. Firth: University of Cambridge
Byron Andrews: STORM Therapeutics Limited, Babraham Research Campus
Alexander J. Whitworth: University of Cambridge, Cambridge Biomedical Campus
Schraga Schwartz: Weizmann Institute of Science
Alan J. Warren: University of Cambridge, Cambridge Biomedical Campus
Michal Minczuk: University of Cambridge, Cambridge Biomedical Campus

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Many cellular processes, including ribosome biogenesis, are regulated through post-transcriptional RNA modifications. Here, a genome-wide analysis of the human mitochondrial transcriptome shows that 2’-O-methylation is limited to residues of the mitoribosomal large subunit (mtLSU) 16S mt-rRNA, introduced by MRM1, MRM2 and MRM3, with the modifications installed by the latter two proteins being interdependent. MRM2 controls mitochondrial respiration by regulating mitoribosome biogenesis. In its absence, mtLSU particles (visualized by cryo-EM at the resolution of 2.6 Å) present disordered RNA domains, partial occupancy of bL36m and bound MALSU1:L0R8F8:mtACP anti-association module, allowing five mtLSU biogenesis intermediates with different intersubunit interface configurations to be placed along the assembly pathway. However, mitoribosome biogenesis does not depend on the methyltransferase activity of MRM2. Disruption of the MRM2 Drosophila melanogaster orthologue leads to mitochondria-related developmental arrest. This work identifies a key checkpoint during mtLSU assembly, essential to maintain mitochondrial homeostasis.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28503-5

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DOI: 10.1038/s41467-022-28503-5

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