TY - JOUR T1 - Synaptic m<sup>6</sup>A Epitranscriptome Reveals Functional Partitioning of Localized Transcripts for Dynamic Tripartite Synapse Modulation JF - bioRxiv DO - 10.1101/221374 SP - 221374 AU - Daria Merkurjev AU - Wan-Ting Hong AU - Kei lida AU - Belinda J Goldie AU - Hitoshi Yamaguti AU - Ikumi Oomoto AU - Takayuki Ohara AU - Shin-ya Kawaguchi AU - Tomoo Hirano AU - Kelsey C Martin AU - Matteo Pellegrini AU - Dan Ohtan Wang Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/17/221374.abstract N2 - A localized transcriptome at the synapse facilitates synapse-, stimulus-, and transcript-specific synthesis of the local proteome in response to neuronal activity. While enzyme-mediated mRNA modifications have been shown to regulate cellular mRNA turnover and translation, the role of these modifications in regulating synaptic RNA has not been studied. We established low-input m6A-seq of synaptosomal RNA to determine the chemically modified local transcriptome in healthy adult mouse forebrain and identified 4,329 selectively enriched m6A RNA peaks in 2,987 genes, which we refer to as the synaptic m6A epitranscriptome (SME). 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 reader YTHDF1 in hippocampal neurons alters expression of SME member Apc, and causes synaptic malfunctions manifesting immature spine morphology and dampened excitatory synaptic transmission concomitant with decreased PSD-95 clustering and GluA1 surface expression. Our findings indicate that chemical modifications of synaptic mRNAs critically contribute to synaptic function. ER -