SERTM2: a neuroactive player in the world of micropeptides

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.

Authors

Institutions

Publication Details

Journal
EMBO Reports
Published
2025-03-19
DOI
https://doi.org/10.1038/s44319-025-00404-w
Citations
1
Primary Topic
Signaling Pathways in Disease
Type
article
Field-Weighted Citation Impact
0.81

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

SERTM2: a neuroactive player in the world of micropeptides

Irene Bozzoni, Carmine Nicoletti, Julie Martone, Michela Lisi et al.
1 citations
EMBO Reports
Signaling Pathways in Disease
0.81
article

SERTM2: a neuroactive player in the world of micropeptides

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

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.

EMBO ReportsVol. 26(8)
Istituto Neurologico Mediterraneo (IT), Italian Institute of Technology (IT), Istituto Pasteur (IT), National Research Council (IT), Sapienza University of Rome (IT)
Consiglio Nazionale delle Ricerche, Istituto Italiano di Tecnologia, Ministero dell'Università e della Ricerca, HORIZON EUROPE European Research Council
Openalex Percentile: Top 30%
Signaling Pathways in Disease
0.81
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.