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

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cam.issuedOnline2022-02-17
dc.contributor.authorRebelo-Guiomar, Pedro
dc.contributor.authorPellegrino, Simone
dc.contributor.authorDent, Kyle C
dc.contributor.authorSas-Chen, Aldema
dc.contributor.authorMiller-Fleming, Leonor
dc.contributor.authorGarone, Caterina
dc.contributor.authorVan Haute, Lindsey
dc.contributor.authorRogan, Jack F
dc.contributor.authorDinan, Adam
dc.contributor.authorFirth, Andrew
dc.contributor.authorAndrews, Byron
dc.contributor.authorWhitworth, Alex
dc.contributor.authorSchwartz, Schraga
dc.contributor.authorWarren, Alan
dc.contributor.authorMinczuk, Michal
dc.contributor.orcidRebelo-Guiomar, Pedro [0000-0002-5060-7519]
dc.contributor.orcidPellegrino, Simone [0000-0001-6302-2774]
dc.contributor.orcidVan Haute, Lindsey [0000-0001-7809-1473]
dc.contributor.orcidDinan, Adam [0000-0003-2812-1616]
dc.contributor.orcidFirth, Andrew [0000-0002-7986-9520]
dc.contributor.orcidWhitworth, Alex [0000-0002-1154-6629]
dc.contributor.orcidWarren, Alan [0000-0001-9277-4553]
dc.contributor.orcidMinczuk, Michal [0000-0001-8242-1420]
dc.date.accessioned2022-02-17T16:00:59Z
dc.date.available2022-02-17T16:00:59Z
dc.date.issued2022-02-17
dc.date.submitted2021-07-27
dc.date.updated2022-02-17T16:00:54Z
dc.descriptionFunder: Kay Kendall Leukaemia Fund (KKLF); doi: https://doi.org/10.13039/501100000402
dc.descriptionFunder: EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011264; Grant(s): Mitobiopath-705560
dc.description.abstractMany 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.
dc.identifier.doi10.17863/CAM.81567
dc.identifier.eissn2041-1723
dc.identifier.issn2041-1723
dc.identifier.others41467-022-28503-5
dc.identifier.other28503
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334157
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/45/500
dc.subject/631/535/1258/1259
dc.subject/631/337/1645
dc.subject/631/80/642/333
dc.subject/631/337/574/1789
dc.subject/101
dc.subject/101/28
dc.subject/101/58
dc.subject/38
dc.subject/38/91
dc.subject/38/77
dc.subject/13
dc.subject/64
dc.subject/64/24
dc.subjectarticle
dc.titleA late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.
dc.typeArticle
dcterms.dateAccepted2022-01-20
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (705560)
pubs.funder-project-idMedical Research Council (MC_UU_00015/4)
pubs.funder-project-idMedical Research Council (MC_UU_00015/6)
pubs.funder-project-idMRC (MR/T012412/1)
pubs.funder-project-idNational Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-022-28503-5

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