Structural basis for the function of long noncoding RNA in neural stem cells.
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Abstract | LncRNA is a -acting regulator of neural stem cell (NSC) differentiation, but the molecular mechanisms by which regulates neurogenesis is unknown. A fundamental step towards mechanistic understanding is to determine whether a lncRNA has folded structure that underlies biological function. Using chemical probing and high-throughput analysis, we determined the secondary structure of folded and . adopts a compact structure with distinct modules and evidence of tertiary interactions. structure is remarkably similar to the conformation. We used locked nucleic acid oligonucleotides to interrogate the entire transcript for function in NSCs and identified regions that when targeted increased neurogenesis - phenocopying knockdown - without decreasing transcript abundance. Our findings provide a structural basis for the role of in neurogenesis and, more broadly, illustrate how structural maps combined with phenotypic data can advance fundamental understanding of lncRNA mechanism. |
Year of Publication | 2025
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Journal | bioRxiv : the preprint server for biology
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Date Published | 09/2025
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ISSN | 2692-8205
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DOI | 10.1101/2025.09.01.671568
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PubMed ID | 40950038
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