The small noncoding vault RNA (vtRNA) is a component of the vault complex, a ribonucleoprotein complex found in most eukaryotes. Emerging evidence suggests that vtRNAs may be involved in the regulation of a variety of cellular functions when unassociated with the vault complex. Here, we demonstrate a novel role for vtRNA in synaptogenesis. Using an in vitro synapse formation model, we show that murine vtRNA (mvtRNA) promotes synapse formation by modulating the MAPK signaling pathway. mvtRNA is transported to the distal region of neurites as part of the vault complex. Interestingly, mvtRNA is released from the vault complex in the neurite by a mitotic kinase Aurora-A–dependent phosphorylation of MVP, a major protein component of the vault complex. mvtRNA binds to and activates MEK1 and thereby enhances MEK1-mediated ERK activation in neurites. These results suggest the existence of a regulatory mechanism of the MAPK signaling pathway by vtRNAs as a new molecular basis for synapse formation.
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January 13 2021
Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling
Shuji Wakatsuki,
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Correspondence to Shuji Wakatsuki: swaka@ncnp.go.jp
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Yoko Takahashi,
Yoko Takahashi
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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Megumi Shibata,
Megumi Shibata
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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Naoki Adachi,
Naoki Adachi
2
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
3
Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Hyogo, Japan
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Tadahiro Numakawa,
Tadahiro Numakawa
2
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
4
Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
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Hiroshi Kunugi,
Hiroshi Kunugi
2
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
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Toshiyuki Araki
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Toshiyuki Araki: taraki@ncnp.go.jp
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Shuji Wakatsuki
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Yoko Takahashi
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Megumi Shibata
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Naoki Adachi
2
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
3
Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Hyogo, Japan
Tadahiro Numakawa
2
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
4
Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan
Hiroshi Kunugi
2
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Toshiyuki Araki
1
Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
Correspondence to Shuji Wakatsuki: swaka@ncnp.go.jp
Toshiyuki Araki: taraki@ncnp.go.jp
Received:
November 18 2019
Revision Received:
September 04 2020
Accepted:
December 02 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
National Center of Neurology and Psychiatry
(NO AWARD)
© 2021 Wakatsuki et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (2): e201911078.
Article history
Received:
November 18 2019
Revision Received:
September 04 2020
Accepted:
December 02 2020
Citation
Shuji Wakatsuki, Yoko Takahashi, Megumi Shibata, Naoki Adachi, Tadahiro Numakawa, Hiroshi Kunugi, Toshiyuki Araki; Small noncoding vault RNA modulates synapse formation by amplifying MAPK signaling. J Cell Biol 1 February 2021; 220 (2): e201911078. doi: https://doi.org/10.1083/jcb.201911078
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