Defective RNA metabolism in motor neurons from Amyotrophic Lateral Scelosis patients
| Project/Area Number |
23700455
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
TSUIJI Hitomi 独立行政法人理化学研究所, 運動ニューロン変性研究チーム, 研究員 (40455358)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ALS / spliceosome / snRNP / TDP-43 / RNA / スプライソソーム / snRNA / SMN / SMA / FUS / RNA代謝 / 筋萎縮性側索硬化症 / 脊髄性筋萎縮症 / splicing |
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| Research Abstract |
Neurodegenerative diseases are characterized by the death of specific type of neurons. The motor neuron diseases amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are caused by dysfunction of TDP-43, RNA-binding protein and SMN, essential for biogenesis of spliceosomal component snRNPs, respectively. However, the defects in RNA metabolism common to these diseases remain unclear. We show that TDP-43 localizes in nuclear gems through association with the SMN complex, and is involved in spliceosome maintenance. Moreover, gems are lost, U snRNA levels are up-regulated and spliceosomal U snRNPs abnormally and extensively accumulate in the nuclei of ALS motor neurons but not in the temporal lobe of FTLD with TDP-43 pathology. Together, these findings indicate that collapse of spliceosome stability is the critical process common to neurodegeneration in ALS and SMA, and may explain cell-type specific vulnerability of motor neurons.
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Spliceosome integrity is defective in motor neuron disease ALS and SMA2013
Author(s)
Tsuiji H., Iguchi Y., Furuya A., Kataoka A., Hatsuta H., Atsuta N., Tanaka F., Hashizume Y., Akatsu H., Murayama S., Sobue G., Yamanaka K
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Journal Title
EMBO Molecular Medicine
Volume: 5(2)
Pages: 221-34
Related Report
Peer Reviewed
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[Journal Article] Spliceosome Integrity is defective in Motor Neuron Diseases, ALS and SMA.2013
Author(s)
Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K
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Journal Title
EMBO Mol Med.
Volume: 5
Pages: 221-234
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Spliceosome integrity is defective in motor neuron disease ALS and SMA2012
Author(s)
Tsuiji H., Iguchi Y., Furuya A., Kataoka A., Hatsuta H., Atsuta N., Tanaka F., Hashizume Y., Akatsu H., Murayama S., Sobue G., Yamanaka K
Organizer
Cold Spring Harbor Meeting : Neurodegenerative Disorders
Place of Presentation
Cold Spring Harbor/NY/USA
Related Report
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[Presentation] TDP-43 in U snRNP regulation2012
Author(s)
Tsuiji H., Kataoka A., Yamanaka K.
Organizer
Keystone Symposia on Molecular and Cellular Biology: Neurodegenerative Diseases: The Molecular and Cellular Basis for Neurodegeneration (F2)
Place of Presentation
Taos, New Mexico, USA
Related Report
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