A Late-stage Assembly Checkpoint of the Human Mitochondrial Ribosome Large Subunit

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Feb 18

PMID 35177605

Authors

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

Affiliations

Soon will be listed here.

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.

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