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

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.

journal_name

Nat Neurosci

journal_title

Nature neuroscience

authors

Merkurjev D,Hong WT,Iida K,Oomoto I,Goldie BJ,Yamaguti H,Ohara T,Kawaguchi SY,Hirano T,Martin KC,Pellegrini M,Wang DO

doi

10.1038/s41593-018-0173-6

subject

Has Abstract

pub_date

2018-07-01 00:00:00

pages

1004-1014

issue

7

eissn

1097-6256

issn

1546-1726

pii

10.1038/s41593-018-0173-6

journal_volume

21

pub_type

杂志文章

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