Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 13111 - 13116 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences |
| Volume | 107 |
| Issue number | 29 |
| DOIs | |
| Publication status | Published - 2010 |
| Externally published | Yes |
Cite this
}
miRNA malfunction causes spinal motor neuron disease. / Haramati, Sharon; Chapnik, Elik; Sztainberg, Yehezkel; Eilam, Raya; Zwang, Raaya; Gershoni, Noga; McGlinn, Edwina; Heiser, Patrick; Wills, Anne-Marie; Wirguin, Itzhak; Rubin, Lee; Misawa, Hidemi; Tabin, Clifford; Brown Jr., Robert; Chen, Alon; Hornstein, Eran.
In: Proceedings of the National Academy of Sciences, Vol. 107, No. 29, 2010, p. 13111 - 13116.Research output: Contribution to journal › Article › Research › peer-review
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
AU - Wills, Anne-Marie
AU - Wirguin, Itzhak
AU - Rubin, Lee
AU - Misawa, Hidemi
AU - Tabin, Clifford
AU - Brown Jr., Robert
AU - Chen, Alon
AU - Hornstein, Eran
PY - 2010
Y1 - 2010
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.
UR - http://www.pnas.org/content/107/29/13111.full.pdf+html
U2 - 10.1073/pnas.1006151107/-/DCSupplemental
DO - 10.1073/pnas.1006151107/-/DCSupplemental
M3 - Article
VL - 107
SP - 13111
EP - 13116
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
SN - 0027-8424
IS - 29
ER -