Human mitochondrial ribosomes can switch their structural RNA composition.

TitleHuman mitochondrial ribosomes can switch their structural RNA composition.
Publication TypeJournal Article
Year of Publication2016
AuthorsRorbach, J, Gao, F, Powell, CA, D'Souza, A, Lightowlers, RN, Minczuk, MA, Chrzanowska-Lightowlers, ZM
JournalProc Natl Acad Sci U S A
Volume113
Issue43
Pagination12198-12201
Date Published2016 Oct 25
ISSN1091-6490
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.

DOI10.1073/pnas.1609338113
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.1609338113
PubMed ID27729525
PubMed Central IDPMC5087001
Grant ListMC_U105697135 / / Medical Research Council / United Kingdom