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Human mitochondrial ribosomes can switch structural tRNAs – but when and why?

a , b , c

RNA Biology

Taylor & Francis

Human, mammalian, Mitochondria, ribosomes, rRNA, tRNA

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      ABSTRACT

      High resolution cryoEM of mammalian mitoribosomes revealed the unexpected presence of mitochondrially encoded tRNA as a structural component of mitochondrial large ribosomal subunit (mt-LSU). Our previously published data identified that only mitochondrial (mt-) tRNAPhe and mt-tRNAVal can be incorporated into mammalian mt-LSU and within an organism there is no evidence of tissue specific variation. When mt-tRNAVal is limiting, human mitoribosomes can integrate mt-tRNAPhe instead to generate a translationally competent monosome. Here we discuss the possible reasons for and consequences of the observed plasticity of the structural mt-tRNA integration. We also indicate potential direction for further research that could help our understanding of the mechanistic and evolutionary aspects of this unprecedented system.

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      Most cited references 40

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      Sequence and organization of the human mitochondrial genome.

      The complete sequence of the 16,569-base pair human mitochondrial genome is presented. The genes for the 12S and 16S rRNAs, 22 tRNAs, cytochrome c oxidase subunits I, II and III, ATPase subunit 6, cytochrome b and eight other predicted protein coding genes have been located. The sequence shows extreme economy in that the genes have none or only a few noncoding bases between them, and in many cases the termination codons are not coded in the DNA but are created post-transcriptionally by polyadenylation of the mRNAs.
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        Animal mitochondrial genomes.

         Jeffrey Boore (1999)
        Animal mitochondrial DNA is a small, extrachromosomal genome, typically approximately 16 kb in size. With few exceptions, all animal mitochondrial genomes contain the same 37 genes: two for rRNAs, 13 for proteins and 22 for tRNAs. The products of these genes, along with RNAs and proteins imported from the cytoplasm, endow mitochondria with their own systems for DNA replication, transcription, mRNA processing and translation of proteins. The study of these genomes as they function in mitochondrial systems-'mitochondrial genomics'-serves as a model for genome evolution. Furthermore, the comparison of animal mitochondrial gene arrangements has become a very powerful means for inferring ancient evolutionary relationships, since rearrangements appear to be unique, generally rare events that are unlikely to arise independently in separate evolutionary lineages. Complete mitochondrial gene arrangements have been published for 58 chordate species and 29 non-chordate species, and partial arrangements for hundreds of other taxa. This review compares and summarizes these gene arrangements and points out some of the questions that may be addressed by comparing mitochondrial systems.
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          Human mitochondrial tRNAs: biogenesis, function, structural aspects, and diseases.

          Mitochondria are eukaryotic organelles that generate most of the energy in the cell by oxidative phosphorylation (OXPHOS). Each mitochondrion contains multiple copies of a closed circular double-stranded DNA genome (mtDNA). Human (mammalian) mtDNA encodes 13 essential subunits of the inner membrane complex responsible for OXPHOS. These mRNAs are translated by the mitochondrial protein synthesis machinery, which uses the 22 species of mitochondrial tRNAs (mt tRNAs) encoded by mtDNA. The unique structural features of mt tRNAs distinguish them from cytoplasmic tRNAs bearing the canonical cloverleaf structure. The genes encoding mt tRNAs are highly susceptible to point mutations, which are a primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. A large number of nuclear factors involved in the biogenesis and function of mt tRNAs have been identified and characterized, including processing endonucleases, tRNA-modifying enzymes, and aminoacyl-tRNA synthetases. These nuclear factors are also targets of pathogenic mutations linked to various diseases, indicating the functional importance of mt tRNAs for mitochondrial activity.
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            Author and article information

            Affiliations
            [a ]The Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University , Newcastle upon Tyne, England, UK
            [b ]Department of Medical Biochemistry and Biophysics, Karolinska Institutet , Retzius väg 8, Stockholm, Sweden
            [c ]MRC Mitochondrial Biology Unit , Wellcome Trust/MRC Building, Hills Road, Cambridge, England, UK
            Author notes
            CONTACT Zofia Chrzanowska-Lightowlers zofia.chrzanowska-lightowlers@ 123456ncl.ac.uk The Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University , Newcastle upon Tyne, NE2 4HH, England UK Michal Minczuk mam@ 123456mrc-mbu.cam.ac.uk , MRC Mitochondrial Biology Unit , Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, England UK
            Journal
            RNA Biol
            RNA Biol
            KRNB
            krnb20
            RNA Biology
            Taylor & Francis
            1547-6286
            1555-8584
            2017
            13 September 2017
            13 September 2017
            : 14
            : 12
            : 1668-1671
            28786741
            5731804
            1356551
            10.1080/15476286.2017.1356551
            © 2017 The Author(s). Published with license by Taylor & Francis Group, LLC

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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            Figures: 1, Tables: 0, Equations: 0, References: 40, Pages: 4
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            Molecular biology

            trna, human, mammalian, mitochondria, ribosomes, rrna

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