Research ExplorerPublicationsCLP1 links tRNA metabolism to progressive motor-neuron loss

CLP1 links tRNA metabolism to progressive motor-neuron loss

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CLP1 links tRNA metabolism to progressive motor-neuron loss. / Hanada, Toshikatsu; Weitzer, Stefan; Mair, Barbara; Bernreuther, Christian; Wainger, Brian J; Ichida, Justin; Hanada, Reiko; Orthofer, Michael; Cronin, Shane J; Komnenovic, Vukoslav; Minis, Adi; Sato, Fuminori; Mimata, Hiromitsu; Yoshimura, Akihiko; Tamir, Ido; Rainer, Johannes; Kofler, Reinhard; Yaron, Avraham; Eggan, Kevin C; Woolf, Clifford J; Glatzel, Markus; Herbst, Ruth; Martinez, Javier; Penninger, Josef M.

In: NATURE, Vol. 495, No. 7442, 28.03.2013, p. 474-80.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hanada, T, Weitzer, S, Mair, B, Bernreuther, C, Wainger, BJ, Ichida, J, Hanada, R, Orthofer, M, Cronin, SJ, Komnenovic, V, Minis, A, Sato, F, Mimata, H, Yoshimura, A, Tamir, I, Rainer, J, Kofler, R, Yaron, A, Eggan, KC, Woolf, CJ, Glatzel, M, Herbst, R, Martinez, J & Penninger, JM 2013, 'CLP1 links tRNA metabolism to progressive motor-neuron loss', NATURE, vol. 495, no. 7442, pp. 474-80. https://doi.org/10.1038/nature11923

APA

Hanada, T., Weitzer, S., Mair, B., Bernreuther, C., Wainger, B. J., Ichida, J., Hanada, R., Orthofer, M., Cronin, S. J., Komnenovic, V., Minis, A., Sato, F., Mimata, H., Yoshimura, A., Tamir, I., Rainer, J., Kofler, R., Yaron, A., Eggan, K. C., ... Penninger, J. M. (2013). CLP1 links tRNA metabolism to progressive motor-neuron loss. NATURE, 495(7442), 474-80. https://doi.org/10.1038/nature11923

Vancouver

Hanada T, Weitzer S, Mair B, Bernreuther C, Wainger BJ, Ichida J et al. CLP1 links tRNA metabolism to progressive motor-neuron loss. NATURE. 2013 Mar 28;495(7442):474-80. https://doi.org/10.1038/nature11923

Bibtex

@article{ca875bac1d104f1ba2353f4a761120f2,
title = "CLP1 links tRNA metabolism to progressive motor-neuron loss",
abstract = "CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1(K/K)) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1(K/K) mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53.",
keywords = "Amyotrophic Lateral Sclerosis, Animals, Animals, Newborn, Axons, Cell Death, Diaphragm, Embryo Loss, Embryo, Mammalian, Exons, Female, Fibroblasts, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Motor Neurons, Muscular Atrophy, Spinal, Neuromuscular Diseases, Oxidative Stress, RNA Processing, Post-Transcriptional, RNA, Transfer, Tyr, Respiration, Spinal Nerves, Transcription Factors, Tumor Suppressor Protein p53, Tyrosine",
author = "Toshikatsu Hanada and Stefan Weitzer and Barbara Mair and Christian Bernreuther and Wainger, {Brian J} and Justin Ichida and Reiko Hanada and Michael Orthofer and Cronin, {Shane J} and Vukoslav Komnenovic and Adi Minis and Fuminori Sato and Hiromitsu Mimata and Akihiko Yoshimura and Ido Tamir and Johannes Rainer and Reinhard Kofler and Avraham Yaron and Eggan, {Kevin C} and Woolf, {Clifford J} and Markus Glatzel and Ruth Herbst and Javier Martinez and Penninger, {Josef M}",
year = "2013",
month = mar,
day = "28",
doi = "10.1038/nature11923",
language = "English",
volume = "495",
pages = "474--80",
journal = "NATURE",
issn = "0028-0836",
publisher = "NATURE PUBLISHING GROUP",
number = "7442",

}

RIS

TY - JOUR

T1 - CLP1 links tRNA metabolism to progressive motor-neuron loss

AU - Hanada, Toshikatsu

AU - Weitzer, Stefan

AU - Mair, Barbara

AU - Bernreuther, Christian

AU - Wainger, Brian J

AU - Ichida, Justin

AU - Hanada, Reiko

AU - Orthofer, Michael

AU - Cronin, Shane J

AU - Komnenovic, Vukoslav

AU - Minis, Adi

AU - Sato, Fuminori

AU - Mimata, Hiromitsu

AU - Yoshimura, Akihiko

AU - Tamir, Ido

AU - Rainer, Johannes

AU - Kofler, Reinhard

AU - Yaron, Avraham

AU - Eggan, Kevin C

AU - Woolf, Clifford J

AU - Glatzel, Markus

AU - Herbst, Ruth

AU - Martinez, Javier

AU - Penninger, Josef M

PY - 2013/3/28

Y1 - 2013/3/28

N2 - CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1(K/K)) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1(K/K) mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53.

AB - CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1(K/K)) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1(K/K) mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53.

KW - Amyotrophic Lateral Sclerosis

KW - Animals

KW - Animals, Newborn

KW - Axons

KW - Cell Death

KW - Diaphragm

KW - Embryo Loss

KW - Embryo, Mammalian

KW - Exons

KW - Female

KW - Fibroblasts

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Motor Neurons

KW - Muscular Atrophy, Spinal

KW - Neuromuscular Diseases

KW - Oxidative Stress

KW - RNA Processing, Post-Transcriptional

KW - RNA, Transfer, Tyr

KW - Respiration

KW - Spinal Nerves

KW - Transcription Factors

KW - Tumor Suppressor Protein p53

KW - Tyrosine

U2 - 10.1038/nature11923

DO - 10.1038/nature11923

M3 - SCORING: Journal article

C2 - 23474986

VL - 495

SP - 474

EP - 480

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7442

ER -