Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts

Daria Merkurjev, Wan Ting Hong, Kei Iida, Ikumi Oomoto, Belinda J. Goldie, Hitoshi Yamaguti, Takayuki Ohara, Shin ya Kawaguchi, Tomoo Hirano, Kelsey C. Martin, Matteo Pellegrini, Dan Ohtan Wang

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

A localized transcriptome at the synapse facilitates synapse-, stimulus- and transcript-specific local protein synthesis in response to neuronal activity. While enzyme-mediated mRNA modifications are known to regulate cellular mRNA turnover, the role of these modifications in regulating synaptic RNA has not been studied. We established low-input m6A-sequencing of synaptosomal RNA to determine the chemically modified local transcriptome in healthy adult mouse forebrains and identified 4,469 selectively enriched m6A sites in 2,921 genes as the synaptic m6A epitranscriptome (SME). The SME is functionally enriched in synthesis and modulation of tripartite synapses and in pathways implicated in neurodevelopmental and neuropsychiatric diseases. Interrupting m6A-mediated regulation via knockdown of readers in hippocampal neurons altered expression of SME member Apc, resulting in synaptic dysfunction including immature spine morphology and dampened excitatory synaptic transmission concomitant with decreased clusters of postsynaptic density-95 (PSD-95) and decreased surface expression of AMPA receptor subunit GluA1. Our findings indicate that chemical modifications of synaptic mRNAs critically contribute to synaptic function.

Original languageEnglish
Pages (from-to)1004-1014
Number of pages11
JournalNature Neuroscience
Volume21
DOIs
Publication statusPublished - Jul 2018
Externally publishedYes

Keywords

  • cellular neuroscience
  • transcriptomics

Cite this

Merkurjev, D., Hong, W. T., Iida, K., Oomoto, I., Goldie, B. J., Yamaguti, H., ... Wang, D. O. (2018). Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts. Nature Neuroscience, 21, 1004-1014. https://doi.org/10.1038/s41593-018-0173-6
Merkurjev, Daria ; Hong, Wan Ting ; Iida, Kei ; Oomoto, Ikumi ; Goldie, Belinda J. ; Yamaguti, Hitoshi ; Ohara, Takayuki ; Kawaguchi, Shin ya ; Hirano, Tomoo ; Martin, Kelsey C. ; Pellegrini, Matteo ; Wang, Dan Ohtan. / Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts. In: Nature Neuroscience. 2018 ; Vol. 21. pp. 1004-1014.
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author = "Daria Merkurjev and Hong, {Wan Ting} and Kei Iida and Ikumi Oomoto and Goldie, {Belinda J.} and Hitoshi Yamaguti and Takayuki Ohara and Kawaguchi, {Shin ya} and Tomoo Hirano and Martin, {Kelsey C.} and Matteo Pellegrini and Wang, {Dan Ohtan}",
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Merkurjev, D, Hong, WT, Iida, K, Oomoto, I, Goldie, BJ, Yamaguti, H, Ohara, T, Kawaguchi, SY, Hirano, T, Martin, KC, Pellegrini, M & Wang, DO 2018, 'Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts', Nature Neuroscience, vol. 21, pp. 1004-1014. https://doi.org/10.1038/s41593-018-0173-6

Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts. / Merkurjev, Daria; Hong, Wan Ting; Iida, Kei; Oomoto, Ikumi; Goldie, Belinda J.; Yamaguti, Hitoshi; Ohara, Takayuki; Kawaguchi, Shin ya; Hirano, Tomoo; Martin, Kelsey C.; Pellegrini, Matteo; Wang, Dan Ohtan.

In: Nature Neuroscience, Vol. 21, 07.2018, p. 1004-1014.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kawaguchi, Shin ya

AU - Hirano, Tomoo

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