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 journalArticle

195 Citations (Scopus)

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 languageEnglish
Pages (from-to)13111-13116
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number29
DOIs
Publication statusPublished - 2010 Jul 20

Keywords

  • ALS
  • Dicer
  • Motor neuron
  • Neurodegeneration
  • microRNA

ASJC Scopus subject areas

  • General

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  • Cite this

    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