The small ORF (smORF)-encoded polypeptide MIRINE promotes neuronal differentiation in vertebrate brain development

MIRINE, an 83–amino acid smORF-encoded polypeptide conserved across 205 vertebrate species, is membrane-associated and promotes neuronal maturation during vertebrate brain development.

• Why it matters: Brain lncRNAs can encode smORF polypeptides, but most SEPs’ functions are unknown, limiting understanding of how neurogenesis balances proliferation and differentiation.
• What they did: Using ribosome profiling and proteomics in zebrafish and mouse brain, the study identified hundreds of translated smORFs and characterized MIRINE’s 83–amino acid sequence, membrane targeting, and neuronal enrichment during neurogenesis.
• The result: Downregulation of Mirine increased cell proliferation and impaired neuronal maturation in neuroblastoma cells, mouse primary cortical neurons and cortex, and the zebrafish forebrain, where MIRINE associates with Synaptogyrin-3 and related membrane proteins.

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