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Publication : SERTM2: a neuroactive player in the world of micropeptides.

First Author  Lisi M Year  2025
Journal  EMBO Rep Volume  26
Issue  8 Pages  2044-2076
PubMed ID  40108405 Mgi Jnum  J:383005
Mgi Id  MGI:8186765 Doi  10.1038/s44319-025-00404-w
Citation  Lisi M, et al. (2025) SERTM2: a neuroactive player in the world of micropeptides. EMBO Rep 26(8):2044-2076
abstractText  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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