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Human mitochondrial ribosomes can switch their structural RNA composition

Lookup NU author(s): Dr Joanna Rorbach, Dr Fei Gao, Emeritus Professor Robert Lightowlers, Emerita Professor Zofia Chrzanowska-LightowlersORCiD

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by National Academy of Sciences, 2016.

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

Publication metadata

Author(s): Rorbach J, Gao F, Powell CA, D'Souza A, Lightowlers RN, Minczuk M, Chrzanowska-Lightowlers ZM

Publication type: Article

Publication status: Published

Journal: Proceedings of the National Academy of Sciences

Year: 2016

Volume: 113

Issue: 43

Pages: 12198-12201

Print publication date: 25/10/2016

Online publication date: 11/10/2016

Acceptance date: 13/09/2016

Date deposited: 06/01/2017

ISSN (print): 0027-8424

ISSN (electronic): 1091-6490

Publisher: National Academy of Sciences

URL: http://dx.doi.org/10.1073/pnas.1609338113

DOI: 10.1073/pnas.1609338113

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