A micropeptide from lncRNA promotes motor neuron subtype specification

Micropeptides derived from small open-reading frames within long noncoding RNAs (lncRNAs) are involved in various biological pathways but their role in neural development and neurodegeneration remain unclear.

The researchers demonstrate that lncRNA A730046J19Rik hosts a conserved small ORF that encodes Sertm2, a 89-amino acid micropeptide.

Sertm2 is predicted to be a conserved transmembrane protein found in both mouse and human, and enriched in the cytoplasm and neurites.

Sertm2 is predominantly enriched in postmitotic motor neurons (MNs) and plays a role in GDNF-mediated regulation of Etv4 expression.

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.

https://www.embopress.org/doi/full/10.1038/s44319-025-00400-0

https://sciencemission.com/micropeptide-promotes-MN-specification