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, Michal Minczuk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number929
JournalNature Communications
Issue number1
StatePublished - Dec 2022


Dive into the research topics of 'A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit'. Together they form a unique fingerprint.

Cite this