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SERTM2：微肽世界中的一种神经活性物质。

SERTM2: a neuroactive player in the world of micropeptides.

作者信息

Lisi Michela, Santini Tiziana, D'Andrea Tiziano, Salvatori Beatrice, Setti Adriano, Paiardini Alessandro, Nutarelli Sofia, Nicoletti Carmine, Pellegrini Flaminia, Fucile Sergio, Bozzoni Irene, Martone Julie

机构信息

Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Rome, Italy.

Center for Life Nano-& Neuro-Science, Fondazione Istituto Italiano di Tecnologia, Rome, Italy.

出版信息

EMBO Rep. 2025 Apr;26(8):2044-2076. doi: 10.1038/s44319-025-00404-w. Epub 2025 Mar 19.

DOI:10.1038/s44319-025-00404-w
PMID:40108405
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12019361/
Abstract

In this study, we analyze the long noncoding RNA, lncMN3, that is predominantly expressed in motor neurons and shows potential coding capabilities. Utilizing custom antibodies, we demonstrate the production of a lncMN3-derived type I transmembrane micropeptide, SERTM2. Patch-clamp experiments performed on both wild-type and SERTM2 knockout motor neurons, differentiated in vitro from mouse embryonic stem cells, show a difference in the resting membrane potential and overall decreased excitability upon SERTM2 depletion. In vivo studies indicate that the absence of the peptide impairs treadmill test performance. At the mechanistic level, we identify a two-pore domain potassium channel, TASK1, known to be a major determinant of the resting membrane potential in motor neurons, as a SERTM2 interactor. Our study characterizes one of the first lncRNA-derived micropeptides involved in neuronal physiology.

摘要

在本研究中，我们分析了主要在运动神经元中表达并具有潜在编码能力的长链非编码RNA——lncMN3。利用定制抗体，我们证明了一种源自lncMN3的I型跨膜微肽SERTM2的产生。对从小鼠胚胎干细胞体外分化而来的野生型和SERTM2基因敲除运动神经元进行的膜片钳实验表明，SERTM2缺失后静息膜电位存在差异，且整体兴奋性降低。体内研究表明，该肽的缺失会损害跑步机测试表现。在机制层面，我们确定了一种双孔结构域钾通道TASK1（已知是运动神经元静息膜电位的主要决定因素）为SERTM2的相互作用分子。我们的研究表征了首批参与神经元生理学的源自长链非编码RNA的微肽之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cb0/12019361/9e85f706e296/44319_2025_404_Fig11_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cb0/12019361/22560e6dd179/44319_2025_404_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cb0/12019361/b7871a918127/44319_2025_404_Fig7_ESM.jpg
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本文引用的文献

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Accurate structure prediction of biomolecular interactions with AlphaFold 3.利用 AlphaFold 3 进行生物分子相互作用的精确结构预测。
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The lncRNA is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons.
该长链非编码 RNA 作为一种局灶性 mRNA 被转运到细胞质中，在神经元中编码一个小肽。
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and encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells.并编码微肽，调节脊椎动物特异性神经细胞中的染色质可及性。
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A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment.lncRNA Lhx1os的基因敲除小鼠模型会导致运动神经元改变和运动功能障碍。
iScience. 2022 Dec 28;26(1):105891. doi: 10.1016/j.isci.2022.105891. eCollection 2023 Jan 20.
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Long non-coding RNAs: definitions, functions, challenges and recommendations.长非编码 RNA：定义、功能、挑战与建议。
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