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Computational prediction and experimental validation identify functionally conserved lncRNAs from zebrafish to human

ABSTRACT: Genome-wide CRISPR screens identified lncRNAs that promote cell proliferation in HeLa, Huh7, and MCF7 cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE240342 | GEO | 2023/10/22

REPOSITORIES: GEO

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Computational prediction and experimental validation identify functionally conserved lncRNAs from zebrafish to human

Project description:Functional studies of long noncoding RNAs (lncRNAs) have long been hindered by a lack of methods to assess their evolution. Here, we present lncHOME (lncRNA Homology Explorer), a computational pipeline that identifies a unique coPARSE-lncRNA class with conserved genomic locations and patterns of RNA binding protein (RBP) binding sites. Remarkably, several hundred human coPARSE-lncRNAs can be evolutionarily traced to zebrafish. Using CRISPR-Cas12a knockout and rescue assays, we found that knocking out many human coPARSE-lncRNAs led to cell proliferation defects that were rescued by predicted zebrafish homologs. Knocking down the coPARSE-lncRNAs in zebrafish embryos caused severe developmental delays that were rescued by human homologs. Moreover, we verified that human, mouse, and zebrafish coPARSE-lncRNA homologs tend to bind similar RBPs with their conserved fuctions relying on specific RBP binding sites. Overall, our study demonstrates a comprehensive approach for studying functional conservation of lncRNAs and implicates numerous lncRNAs in regulating cellular physiology.

2024-01-26 | PXD046452 | Pride