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Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12198-12201. Epub 2016 Oct 11.

Human mitochondrial ribosomes can switch their structural RNA composition.

Author information

1
Medical Research Council Mitochondrial Biology Unit, Wellcome Trust, Cambridge CB2 0XY, United Kingdom.
2
The Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
3
The Wellcome Trust Centre for Mitochondrial Research, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
4
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.
5
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.

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-tRNAVal compared with the porcine use of mt-tRNAPhe We 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-tRNAVal are depleted. Our data demonstrate that only mt-tRNAVal or mt-tRNAPhe are 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-tRNAVal are reduced, human mitoribosome biogenesis displays an adaptive response by switching to the incorporation of mt-tRNAPhe to generate translationally competent machinery.

KEYWORDS:

mammalian mitochondria; mitochondrial protein synthesis; rRNA; ribosomes; tRNA

PMID:
27729525
PMCID:
PMC5087001
DOI:
10.1073/pnas.1609338113
[Indexed for MEDLINE]
Free PMC Article

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