Synaptic function in neurons is modulated by local translation of mRNAs that are transported to distal portions of axons and dendrites. The metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) is broadly expressed across cell types, almost exclusively as a nuclear long noncoding RNA. We found that in differentiating neurons, a portion of Malat1 RNA redistributes to the cytoplasm. Depletion of Malat1 using antisense oligonucleotides (ASOs) stimulates the expression of particular pre- and postsynaptic proteins, implicating Malat1 in their regulation. Neuronal Malat1 is localized in puncta of both axons and dendrites that costain with Staufen1 protein, similar to neuronal RNA granules formed by locally translated mRNAs. Ribosome profiling of cultured mouse cortical neurons identified ribosome footprints within a 5′ region of Malat1 containing short open reading frames. The upstream-most reading frame (M1) of the Malat1 locus was linked to the GFP-coding sequence in mouse embryonic stem cells. When these gene-edited cells were differentiated into glutamatergic neurons, the M1-GFP fusion protein was expressed. Antibody staining for the M1 peptide confirmed its presence in wild-type neurons and showed that M1 expression was enhanced by synaptic stimulation with KCl. Our results indicate that Malat1 serves as a cytoplasmic coding RNA in the brain that is both modulated by and modulates synaptic function.

中文翻译：

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lncRNA Malat1 作为编码神经元小肽的局部 mRNA 被运输到细胞质


神经元中的突触功能通过 mRNA 的局部翻译进行调节，这些 mRNA 被转运到轴突和树突的远端部分。转移相关肺腺癌转录物 1 (MALAT1) 在各种细胞类型中广泛表达，几乎完全作为核长非编码 RNA。我们发现，在分化的神经元中，Malat1 RNA 的一部分重新分配到细胞质。使用反义寡核苷酸 (ASO) 耗尽 Malat1 会刺激特定突触前和突触后蛋白质的表达，表明 Malat1 参与其调节。神经元 Malat1 位于轴突和树突的斑点中，与 Staufen1 蛋白共存，类似于由局部翻译的 mRNA 形成的神经元 RNA 颗粒。对培养的小鼠皮质神经元的核糖体分析鉴定出 Malat1 5' 区域内包含短开放阅读框的核糖体足迹。 Malat1 基因座的最上游阅读框 (M1) 与小鼠胚胎干细胞中的 GFP 编码序列相连。当这些基因编辑的细胞分化为谷氨酸能神经元时，M1-GFP融合蛋白被表达。 M1 肽的抗体染色证实了它在野生型神经元中的存在，并表明 KCl 突触刺激可增强 M1 表达。我们的结果表明，Malat1 作为大脑中的细胞质编码 RNA，既受突触功能调节，又调节突触功能。