HomeDate: 2025-04-29
A study led by Dr. Jun-An Chen’s group at the Institute of Molecular Biology, Academia Sinica, has revealed a previously unrecognized micropeptide embedded within a misannotated long noncoding RNA (lncRNA). Motor neuron diversity in the spinal cord is crucial for coordinated movement, driven by a complex mix of internal programs and external cues. Dr. Jun-An Chen’s team, known for pioneering work on noncoding RNAs, has now uncovered a surprising discovery—a misannotated long noncoding RNA (lncRNA) that actually encodes a micropeptide named Sertm2.
Highly expressed in embryonic spinal motor neurons, Sertm2 had remained unnoticed until now. Using a combination of embryonic stem cell and animal models, the team showed that deleting Sertm2 did not affect the generic motor neurons but selectively impaired certain subtypes, leading to motor coordination defects in mice. The culprit? Disrupted signaling of GDNF, a key neurotrophic factor essential for motor neuron health and a target in neurodegenerative disease research. Strikingly, reintroducing only Sertm2 micropeptide using lentiviral vectors restored normal motor neuron subtype production in the entire lncRNA genome locus, highlighting its critical role in neuronal development. The peptide’s function was also validated in human iPSC-derived motor neurons, confirming its evolutionary conservation.
This study not only redefines how we view so-called “noncoding” RNAs but also positions micropeptides like Sertm2 as promising therapeutic tools and biomarkers in neurological disease and regenerative medicine.
The study has been published in EMBO Reports (IF 7.7, 2025) on March 19, 2025. The study’s primary author, Fang-Yu Hsu, is a Ph.D. student in the Genome and SystemsBiology Program at Academia Sinica and National Taiwan University. The research team also included Dr. Ya-Ping Yen, Hung-Chi Fan, and Mien Chang. This work was supported by Academia Sinica, the National Science and Technology Council, and the National HealthResearch Institutes of Taiwan.
