Sertm2 is a conserved micropeptide that promotes GDNF-mediated motor neuron subtype specification.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-03-19 DOI:10.1038/s44319-025-00400-0

Fang-Yu Hsu, Ya-Ping Yen, Hung-Chi Fan, Mien Chang, Jun-An Chen

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引用次数: 0

Abstract

Small open-reading frame-encoded micropeptides within long noncoding RNAs (lncRNAs) are often overlooked due to their small size and low abundance. However, emerging evidence links these micropeptides to various biological pathways, though their roles in neural development and neurodegeneration remain unclear. Here, we investigate the function of murine micropeptide Sertm2, encoded by the lncRNA A730046J19Rik, during spinal motor neuron (MN) development. Sertm2 is predicted to be a conserved transmembrane protein found in both mouse and human, with subcellular analysis revealing that it is enriched in the cytoplasm and neurites. By generating C terminally Flag-tagged Sertm2 and expressing it from the A730046J19Rik locus, we demonstrate that the Sertm2 micropeptide localizes in spinal MNs in mice. The GDNF signaling-induced Etv4⁺ motor pool is impaired in Sertm2 knockout mice, which display motor nerve arborization defects that culminate in impaired motor coordination and muscle weakness. Similarly, human SERTM2 knockout iPSC-derived MNs also display reduced ETV4⁺ motor pools, highlighting that Sertm2 is a novel, evolutionarily conserved micropeptide essential for maintaining GDNF-induced MN subtype identity.

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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.