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

doi:https://doi.org/10.1038/s41467-022-28503-5

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

Tel Aviv University, Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	929
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28503-5
State	Published - Dec 2022

All Science Journal Classification (ASJC) codes

General Chemistry
General
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.1038/s41467-022-28503-5

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Rebelo-Guiomar, P., Pellegrino, S., Dent, K. C., Sas-Chen, A., Miller-Fleming, L., Garone, C., Van Haute, L., Rogan, J. F., Dinan, A., Firth, A. E., Andrews, B., Whitworth, A. J., Schwartz, S., Warren, A. J., & Minczuk, M. (2022). A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit. Nature Communications, 13(1), Article 929. https://doi.org/10.1038/s41467-022-28503-5

@article{07ec1af5b05847b98a8973f8c853f08b,

title = "A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit",

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{\textquoteright}-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 {\AA}) 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.",

author = "Pedro Rebelo-Guiomar and Simone Pellegrino and Dent, {Kyle C.} and Aldema Sas-Chen and Leonor Miller-Fleming and Caterina Garone and {Van Haute}, Lindsey and Rogan, {Jack F.} and Adam Dinan and Firth, {Andrew E.} and Byron Andrews and Whitworth, {Alexander J.} and Schraga Schwartz and Warren, {Alan J.} and Michal Minczuk",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "https://doi.org/10.1038/s41467-022-28503-5",

language = "الإنجليزيّة",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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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', Nature Communications, vol. 13, no. 1, 929. https://doi.org/10.1038/s41467-022-28503-5

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

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.

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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 -

A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit

Abstract

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