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Computational prediction and experimental validation identify functionally conserved lncRNAs from zebrafish to human.
Wenze Huang1,2,3, Tuanlin Xiong1,2,3, Yuting Zhao4,5
1MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Nature Genetics
|January 10, 2024
Summary
We developed lncRNA Homology Explorer (lncHOME) to study long noncoding RNA (lncRNA) evolution. This tool identified conserved lncRNAs between humans and zebrafish, revealing their crucial roles in cell proliferation and development.
Area of Science:
- Genomics and Molecular Biology
- Evolutionary Biology
- Bioinformatics
Background:
- Studying the evolution of long noncoding RNAs (lncRNAs) is challenging due to a lack of effective methods.
- Understanding lncRNA functional conservation across species is critical for deciphering their roles in vertebrate physiology.
Purpose of the Study:
- To introduce lncRNA Homology Explorer (lncHOME), a novel computational pipeline for identifying evolutionarily conserved lncRNAs.
- To investigate the functional conservation of a specific class of lncRNAs, termed co-expressed and co-transcribed lncRNAs (coPARSE-lncRNAs), across vertebrate species.
Main Methods:
- Development of the lncRNA Homology Explorer (lncHOME) pipeline to identify lncRNAs with conserved genomic locations and RNA-binding protein (RBP) binding sites.
- Utilized CRISPR-Cas12a knockout and rescue assays in human cell lines to assess the function of coPARSE-lncRNAs.
- Employed knockdown and rescue experiments in zebrafish embryos to validate the functional conservation of identified lncRNA homologs.
Main Results:
- Identified several hundred human coPARSE-lncRNAs with conserved genomic locations and RBP binding patterns traceable to zebrafish.
- Demonstrated that knockout of human coPARSE-lncRNAs resulted in cell proliferation defects, which were rescued by zebrafish homologs.
- Showcased that knockdown of coPARSE-lncRNAs in zebrafish embryos led to developmental delays, rescued by human homologs, and confirmed conserved RBP binding and function across species.
Conclusions:
- The lncHOME pipeline provides a robust approach for assessing the functional evolution of lncRNAs.
- coPARSE-lncRNAs play significant roles in regulating fundamental biological processes such as cell proliferation and embryonic development.
- This study highlights the functional conservation of lncRNAs and their importance in vertebrate physiology.
