miRNA malfunction causes spinal motor neuron disease

Sharon Haramati; Elik Chapnik; Yehezkel Sztainberg; Raya Eilam; Raaya Zwang; Noga Gershoni; Edwina McGlinn; Patrick W. Heiser; Anne Marie Wills; Itzhak Wirguin; Lee L. Rubin; Hidemi Misawa; Clifford J. Tabin; Robert Brown; Alon Chen; Eran Hornstein

doi:10.1073/pnas.1006151107

miRNA malfunction causes spinal motor neuron disease

Sharon Haramati, Elik Chapnik, Yehezkel Sztainberg, Raya Eilam, Raaya Zwang, Noga Gershoni, Edwina McGlinn, Patrick W. Heiser, Anne Marie Wills, Itzhak Wirguin, Lee L. Rubin, Hidemi Misawa, Clifford J. Tabin, Robert Brown, Alon Chen, Eran Hornstein

Research output: Contribution to journal › Article › peer-review

253 Scopus citations

Abstract

Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do not process miRNA in SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9-based regulatory mechanisms in adult neurons and neurodegenerative states.

Original language	English
Pages (from-to)	13111-13116
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	107
Issue number	29
DOIs	https://doi.org/10.1073/pnas.1006151107
State	Published - 20 Jul 2010

Keywords

ALS
Dicer
Motor neuron
Neurodegeneration
microRNA

ASJC Scopus subject areas

General

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10.1073/pnas.1006151107

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Haramati, S., Chapnik, E., Sztainberg, Y., Eilam, R., Zwang, R., Gershoni, N., McGlinn, E., Heiser, P. W., Wills, A. M., Wirguin, I., Rubin, L. L., Misawa, H., Tabin, C. J., Brown, R., Chen, A., & Hornstein, E. (2010). miRNA malfunction causes spinal motor neuron disease. Proceedings of the National Academy of Sciences of the United States of America, 107(29), 13111-13116. https://doi.org/10.1073/pnas.1006151107

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title = "miRNA malfunction causes spinal motor neuron disease",

abstract = "Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do not process miRNA in SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9-based regulatory mechanisms in adult neurons and neurodegenerative states.",

keywords = "ALS, Dicer, Motor neuron, Neurodegeneration, microRNA",

author = "Sharon Haramati and Elik Chapnik and Yehezkel Sztainberg and Raya Eilam and Raaya Zwang and Noga Gershoni and Edwina McGlinn and Heiser, {Patrick W.} and Wills, {Anne Marie} and Itzhak Wirguin and Rubin, {Lee L.} and Hidemi Misawa and Tabin, {Clifford J.} and Robert Brown and Alon Chen and Eran Hornstein",

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doi = "10.1073/pnas.1006151107",

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Haramati, S, Chapnik, E, Sztainberg, Y, Eilam, R, Zwang, R, Gershoni, N, McGlinn, E, Heiser, PW, Wills, AM, Wirguin, I, Rubin, LL, Misawa, H, Tabin, CJ, Brown, R, Chen, A & Hornstein, E 2010, 'miRNA malfunction causes spinal motor neuron disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 29, pp. 13111-13116. https://doi.org/10.1073/pnas.1006151107

TY - JOUR

T1 - miRNA malfunction causes spinal motor neuron disease

AU - Haramati, Sharon

AU - Chapnik, Elik

AU - Sztainberg, Yehezkel

AU - Eilam, Raya

AU - Zwang, Raaya

AU - Gershoni, Noga

AU - McGlinn, Edwina

AU - Heiser, Patrick W.

AU - Wills, Anne Marie

AU - Wirguin, Itzhak

AU - Rubin, Lee L.

AU - Misawa, Hidemi

AU - Tabin, Clifford J.

AU - Brown, Robert

AU - Chen, Alon

AU - Hornstein, Eran

PY - 2010/7/20

Y1 - 2010/7/20

N2 - Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do not process miRNA in SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9-based regulatory mechanisms in adult neurons and neurodegenerative states.

AB - Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do not process miRNA in SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9-based regulatory mechanisms in adult neurons and neurodegenerative states.

KW - ALS

KW - Dicer

KW - Motor neuron

KW - Neurodegeneration

KW - microRNA

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U2 - 10.1073/pnas.1006151107

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AN - SCOPUS:77955599311

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 29

ER -

miRNA malfunction causes spinal motor neuron disease

Abstract

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