title: Human mitochondrial ribosomes can switch their structural RNA composition.
abstract: The recent developments in cryo-EM have revolutionized our access to previously refractory structures. In particular, such studies of mammalian mitoribosomes have confirmed the absence of any 5S rRNA species and revealed the unexpected presence of a mitochondrially encoded tRNA (mt-tRNA) that usurps this position. Although the cryo-EM structures resolved the conundrum of whether mammalian mitoribosomes contain a 5S rRNA, they introduced a new dilemma: Why do human and porcine mitoribosomes integrate contrasting mt-tRNAs? Human mitoribosomes have been shown to integrate mt-tRNAValcompared with the porcine use of mt-tRNAPheWe have explored this observation further. Our studies examine whether a range of mt-tRNAs are used by different mammals, or whether the mt-tRNA selection is strictly limited to only these two species of the 22 tRNAs encoded by the mitochondrial genome (mtDNA); whether there is tissue-specific variation within a single organism; and what happens to the human mitoribosome when levels of the mt-tRNAValare depleted. Our data demonstrate that only mt-tRNAValor mt-tRNAPheare found in the mitoribosomes of five different mammals, each mammal favors the same mt-tRNA in all tissue types, and strikingly, when steady-state levels of mt-tRNAValare reduced, human mitoribosome biogenesis displays an adaptive response by switching to the incorporation of mt-tRNAPheto generate translationally competent machinery.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust, Cambridge CB2 0XY, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rorbach
authors.affiliation: The Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust, Cambridge CB2 0XY, United Kingdom.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Powell
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust, Cambridge CB2 0XY, United Kingdom.
authors.forename: Aaron
authors.initials: A
authors.lastname: D'Souza
authors.affiliation: The Wellcome Trust Centre for Mitochondrial Research, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Wellcome Trust, Cambridge CB2 0XY, United Kingdom; zofia.chrzanowska-lightowlers@ncl.ac.uk mam@mrc-mbu.cam.ac.uk.
authors.forename: Michal
authors.initials: M
authors.lastname: Minczuk
authors.affiliation: The Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom; The Wellcome Trust Centre for Mitochondrial Research, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom zofia.chrzanowska-lightowlers@ncl.ac.uk mam@mrc-mbu.cam.ac.uk.
authors.forename: Zofia M
authors.initials: ZM
authors.lastname: Chrzanowska-Lightowlers
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D000069396:Mitochondrial Ribosomes / Q000737:chemistry* / Q000648:ultrastructure; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012341:RNA, Ribosomal, 5S / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics / Q000648:ultrastructure*; D013552:Swine
chemical_list: D004272:DNA, Mitochondrial; D012341:RNA, Ribosomal, 5S; D012343:RNA, Transfer
keywords: mammalian mitochondria; mitochondrial protein synthesis; rRNA; ribosomes; tRNA