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A bifunctional, moonlighting RNA coordinates pathways to regulate human embryonic development [snRNA-seq]

GSE275697 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/02/20 Platform GPL30173Platform GPL24676
Summary
Early embryogenesis and cellular differentiation require complex choreography between nuclear and cytoplasmic pathways. Through integrative analysis and a short open reading frame functional screen, sORF-seq, we identified lncPRESS1, a bifunctional long-non-coding RNA that also encodes a microprotein. In the nucleus, lncPRESS1 binds BRG1 to regulate chromatin remodeling and modulate the expression of pluripotency and differentiation genes. In the cytoplasm, lncPRESS1 is translated into a microprotein that binds to IFT57, regulating ciliogenesis and SHH signaling pathways to control lineage commitment. Together, these results reveal a novel mechanism where the dual functions of lncPRESS1 simultaneously coordinate chromatin remodeling and signaling pathways. This coordination co-regulates the initial developmental decisions specifying neuroectoderm and mesoderm fates during human embryonic development, underscoring the underappreciated complexity of multifunctional RNAs.
Published in
Functional landscape of non-canonical open reading frames in coordinating cell fate
Zhu K, Li WC, Liu J et al. · Molecular cell 2026 · PMID 41785859 · doi:10.1016/j.molcel.2026.02.010
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Also filed as BioProject PRJNA1152583 and SRA study SRP528703. Searching any of these in the dataset finder brings you back here.

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