TY - JOUR
T1 - A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit
AU - Rebelo-Guiomar, Pedro
AU - Pellegrino, Simone
AU - Dent, Kyle C.
AU - Sas-Chen, Aldema
AU - Miller-Fleming, Leonor
AU - Garone, Caterina
AU - Van Haute, Lindsey
AU - Rogan, Jack F.
AU - Dinan, Adam
AU - Firth, Andrew E.
AU - Andrews, Byron
AU - Whitworth, Alexander J.
AU - Schwartz, Schraga
AU - Warren, Alan J.
AU - Minczuk, Michal
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124777350&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-022-28503-5
DO - https://doi.org/10.1038/s41467-022-28503-5
M3 - مقالة
C2 - 35177605
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 929
ER -