Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria

Taru Hilander, Xiao-Long Zhou, Svetlana Konovalova, Fu-Ping Zhang, Liliya Euro, Dmitri Shilov, Matti Poutanen, Joseph Chihade, En-Duo Wang, Henna Tyynismaa

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.
Alkuperäiskielienglanti
LehtiNucleic Acids Research
Vuosikerta46
Numero2
Sivut849–860
Sivumäärä12
ISSN0305-1048
DOI - pysyväislinkit
TilaJulkaistu - 2018
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3111 Biolääketieteet

Lainaa tätä

Hilander, Taru ; Zhou, Xiao-Long ; Konovalova, Svetlana ; Zhang, Fu-Ping ; Euro, Liliya ; Shilov, Dmitri ; Poutanen, Matti ; Chihade, Joseph ; Wang, En-Duo ; Tyynismaa, Henna. / Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria. Julkaisussa: Nucleic Acids Research. 2018 ; Vuosikerta 46, Nro 2. Sivut 849–860.
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title = "Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria",
abstract = "Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.",
keywords = "3111 Biomedicine",
author = "Taru Hilander and Xiao-Long Zhou and Svetlana Konovalova and Fu-Ping Zhang and Liliya Euro and Dmitri Shilov and Matti Poutanen and Joseph Chihade and En-Duo Wang and Henna Tyynismaa",
year = "2018",
doi = "10.1093/nar/gkx1231",
language = "English",
volume = "46",
pages = "849–860",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
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Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria. / Hilander, Taru; Zhou, Xiao-Long; Konovalova, Svetlana; Zhang, Fu-Ping; Euro, Liliya; Shilov, Dmitri; Poutanen, Matti; Chihade, Joseph; Wang, En-Duo; Tyynismaa, Henna.

julkaisussa: Nucleic Acids Research, Vuosikerta 46, Nro 2, 2018, s. 849–860.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria

AU - Hilander, Taru

AU - Zhou, Xiao-Long

AU - Konovalova, Svetlana

AU - Zhang, Fu-Ping

AU - Euro, Liliya

AU - Shilov, Dmitri

AU - Poutanen, Matti

AU - Chihade, Joseph

AU - Wang, En-Duo

AU - Tyynismaa, Henna

PY - 2018

Y1 - 2018

N2 - Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.

AB - Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms.

KW - 3111 Biomedicine

U2 - 10.1093/nar/gkx1231

DO - 10.1093/nar/gkx1231

M3 - Article

VL - 46

SP - 849

EP - 860

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 2

ER -