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

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human) Danio Rerio (zebrafish) (brachydanio Rerio) Mus Musculus (mouse)

TISSUE(S): Embryo, Embryonic Stem Cell, Hela Cell

SUBMITTER: Wenze Huang  

LAB HEAD: Qiangfeng Cliff Zhang

PROVIDER: PXD046452 | Pride | 2024-01-26

REPOSITORIES: Pride