Summary information and primary citation
- PDB-id
-
7qh7;
DSSR-derived features in text and
JSON formats
- Class
- ribosome
- Method
- cryo-EM (2.89 Å)
- Summary
- cryo-EM structure of the human mtlsu assembly
intermediate upon mrm2 depletion - class 4
- Reference
-
Rebelo-Guiomar P, Pellegrino S, Dent KC, Sas-Chen A,
Miller-Fleming L, Garone C, Van Haute L, Rogan JF, Dinan
A, Firth AE, Andrews B, Whitworth AJ, Schwartz S, Warren
AJ, Minczuk M (2022): "A
late-stage assembly checkpoint of the human mitochondrial
ribosome large subunit." Nat Commun,
13, 929. doi: 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.
