A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.
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Authors
Dent, Kyle C
Sas-Chen, Aldema
Miller-Fleming, Leonor
Garone, Caterina
Rogan, Jack F
Dinan, Adam
Andrews, Byron
Schwartz, Schraga
Publication Date
2022-02-17Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Rebelo-Guiomar, P., Pellegrino, S., Dent, K. C., Sas-Chen, A., Miller-Fleming, L., Garone, C., Van Haute, L., et al. (2022). A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-28503-5
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.
Keywords
Animals, Humans, Drosophila melanogaster, Methyltransferases, Drosophila Proteins, Ribosomal Proteins, RNA, Ribosomal, 16S, Protein Biosynthesis, Methylation, Male, Ribosome Subunits, Large, Gene Knockout Techniques, HEK293 Cells, Mitochondrial Ribosomes
Sponsorship
Wellcome Trust (100140/Z/12/Z)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (705560)
Medical Research Council (MC_UU_00015/4)
Medical Research Council (MC_UU_00015/6)
MRC (MR/T012412/1)
National Institute for Health Research (IS-BRC-1215-20014)
Identifiers
35177605, PMC8854578
External DOI: https://doi.org/10.1038/s41467-022-28503-5
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335276
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