SERTM2: a neuroactive player in the world of micropeptides.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-04-01 Epub Date: 2025-03-19 DOI:10.1038/s44319-025-00404-w

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

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引用次数: 0

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.

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SERTM2：微肽世界中的神经活性参与者。

在这项研究中，我们分析了长链非编码RNA lncMN3，它主要在运动神经元中表达，并显示出潜在的编码能力。利用定制抗体，我们证明了lncmn3衍生的I型跨膜微肽SERTM2的产生。在小鼠胚胎干细胞体外分化的野生型和敲除SERTM2的运动神经元上进行的膜片钳实验显示，SERTM2缺失后静息膜电位和总体兴奋性下降存在差异。体内研究表明，肽的缺失会损害跑步机测试的表现。在机制水平上，我们确定了一个双孔结构域钾通道TASK1，它是运动神经元静息膜电位的主要决定因素，是SERTM2的相互作用因子。我们的研究描述了第一个lncrna衍生的微肽参与神经元生理学。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.