@article{ef43f0354e0243e88bcfcdc11adfdbef,
title = "Structures of the human mitochondrial ribosome in native states of assembly",
abstract = "Mammalian mitochondrial ribosomes (mitoribosomes) have less rRNA content and 36 additional proteins compared with the evolutionarily related bacterial ribosome. These differences make the assembly of mitoribosomes more complex than the assembly of bacterial ribosomes, but the molecular details of mitoribosomal biogenesis remain elusive. Here, we report the structures of two late-stage assembly intermediates of the human mitoribosomal large subunit (mt-LSU) isolated from a native pool within a human cell line and solved by cryo-EM to 3-resolution. Comparison of the structures reveals insights into the timing of rRNA folding and protein incorporation during the final steps of ribosomal maturation and the evolutionary adaptations that are required to preserve biogenesis after the structural diversification of mitoribosomes. Furthermore, the structures redefine the ribosome silencing factor (RsfS) family as multifunctional biogenesis factors and identify two new assembly factors (L0R8F8 and mt-ACP) not previously implicated in mitoribosomal biogenesis.",
author = "Alan Brown and Sorbhi Rathore and Dari Kimanius and Shintaro Aibara and Bai, {Xiao Chen} and Joanna Rorbach and Alexey Amunts and V. Ramakrishnan",
note = "Funding Information: This work was funded by the Swedish Research Council (NT_2015-04107), the Swedish Foundation for Strategic Research (Future Leaders Grant FFL15-0325), and the Ragnar S{\"o}derberg Foundation (Fellowship in Medicine M44/16) to A.A., and the UK Medical Research Council (MC_U105184332), the Wellcome Trust (Senior Investigator Award WT096570), and the Agouron Institute and the Louis-Jeantet Foundation to V.R. S.A. was supported by a FEBS Long-Term Fellowship. J.R. and A.A. were supported by Marie Sklodowska Curie Actions (International Career Grant 2015-00579). Funding to M. Minczuk (MC_U105697135) supported the research activities of S.R. and J.R. at the MRC Mitochondrial Biology Unit. Cryo-EM data were collected at the MRC Laboratory of Molecular Biology and the Swedish National Facility. We thank S. Chen, J. Conrad, M. Carroni, and C. Savva for help with data collection; S. Peak-Chew, G. Degliesposti, M. Skehel, and F. Stengel for MS analysis; J. Grimmett, T. Darling, and S. Fleischmann for computing support; D. Marks for help with evolutionary couplings; M. Minczuk for discussions and unpublished data; and C. Tate (MRC Laboratory of Molecular Biology) for providing cells.",
year = "2017",
month = oct,
day = "5",
doi = "10.1038/nsmb.3464",
language = "English (US)",
volume = "24",
pages = "866--869",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "10",
}