Functional landscape of non-canonical open reading frames in coordinating cell fate - PubMed
5 days ago
- #microprotein
- #bifunctional RNA
- #lineage commitment
- The human genome contains many unannotated short open reading frames (sORFs) that may encode microproteins, but their roles are not well understood.
- Researchers developed sORF-seq, a functional screen, to identify sORF-encoded microproteins that regulate cellular differentiation.
- lncPRESS1 was discovered as a key regulator of cell fate, functioning both as a long non-coding RNA (lncRNA) in the nucleus and as an mRNA translated into a microprotein in the cytoplasm.
- In the nucleus, lncPRESS1 guides the genomic distribution of SWI/SNF and orchestrates developmental gene expression programs.
- In the cytoplasm, the lncPRESS1 microprotein directs lineage commitment through Sonic hedgehog (SHH) signaling pathways and interactions with the primary cilium.
- This dual functionality allows lncPRESS1 to coordinate nuclear and cytoplasmic regulatory networks, influencing early embryogenesis and human brain development.
- The study reveals a new paradigm for non-canonical ORFs in coordinating complex pathways, expanding the understanding of the functional genome beyond traditional coding genes.