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Interconnected assembly factors regulate the biogenesis of mitoribosomal large subunit
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0001-8920-017X
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0003-2221-482X
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0002-6096-9169
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Number of Authors: 62021 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 40, no 6, article id e106292Article in journal (Refereed) Published
Abstract [en]

Mitoribosomes consist of ribosomal RNA and protein components, coordinated assembly of which is critical for function. We used mitoribosomes from Trypanosoma brucei with reduced RNA and increased protein mass to provide insights into the biogenesis of the mitoribosomal large subunit. Structural characterization of a stable assembly intermediate revealed 22 assembly factors, some of which have orthologues/counterparts/homologues in mammalian genomes. These assembly factors form a protein network that spans a distance of 180 angstrom, shielding the ribosomal RNA surface. The central protuberance and L7/L12 stalk are not assembled entirely and require removal of assembly factors and remodeling of the mitoribosomal proteins to become functional. The conserved proteins GTPBP7 and mt-EngA are bound together at the subunit interface in proximity to the peptidyl transferase center. A mitochondrial acyl-carrier protein plays a role in docking the L1 stalk, which needs to be repositioned during maturation. Additional enzymatically deactivated factors scaffold the assembly while the exit tunnel is blocked. Together, this extensive network of accessory factors stabilizes the immature sites and connects the functionally important regions of the mitoribosomal large subunit.

Place, publisher, year, edition, pages
2021. Vol. 40, no 6, article id e106292
Keywords [en]
assembly, mitochondria, mitoribosome, translation, trypanosoma
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-192572DOI: 10.15252/embj.2020106292ISI: 000617216000001PubMedID: 33576519Scopus ID: 2-s2.0-85100839371OAI: oai:DiVA.org:su-192572DiVA, id: diva2:1547773
Funder
Swedish Foundation for Strategic Research, FFL15:0325Ragnar Söderbergs stiftelse, M44/16Swedish Cancer Society, 2017/1041Knut and Alice Wallenberg Foundation, 2018.0080Available from: 2021-04-28 Created: 2021-04-28 Last updated: 2022-08-11Bibliographically approved
In thesis
1. On the Origin and Evolution of the Mitochondrial Ribosome
Open this publication in new window or tab >>On the Origin and Evolution of the Mitochondrial Ribosome
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Den mitokondriella ribosomens ursprung och utveckling
Abstract [en]

The ribosome is among the most ancient, intricate and well studied macromolecular complexes in biology. Predating the earliest divergence of life, its core molecular structure has remained mostly unchanged for more than three billion years. In stark contrast to its monolithic ancestor, the mitochondrial ribosome represents one of the most architecturally diverse protein complexes investigated. This work is an attempt at reconciling these two paradigms. In this thesis I first briefly cover the evolutionary history of the mitochondrial ribosome: from its ancient origins, through the process of Eukaryogenesis and the development of mitochondria, to its current state. Following this I present a comprehensive and integrated comparative analysis of the current mitoribosomal structures. Using these structural observations as a starting point I then summarise the current knowledge regarding the evolutionary trends of mitochondrial ribosomes. Finally I review and discuss potential genetic mechanisms and evolutionary pressures which could have produced such a vibrant diversity of structures. Together with this analysis I present monosome structures from the ciliate Tetrahymena thermophila and chlorophycean Polytomella magna together with an assembly intermediate of the large subunit from Trypanosoma brucei. Together, I hope to demonstrate the impact of the unique mitochondrial environment on the evolution of the mitochondrial ribosome. 

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2022. p. 86
Keywords
Ribosome, mitochondria, evolution, structural biology
National Category
Biochemistry Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-203931 (URN)978-91-7911-878-5 (ISBN)978-91-7911-879-2 (ISBN)
Public defence
2022-05-20, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 13:30 (English)
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Supervisors
Available from: 2022-04-27 Created: 2022-04-15 Last updated: 2025-02-20Bibliographically approved

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Tobiasson, VictorGahura, OndřejAibara, ShintaroBaradaran, RozbehZiková, AlenaAmunts, Alexey

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