2024-11-07 ニューヨーク大学 (NYU)
<関連情報>
- https://www.nyu.edu/about/news-publications/news/2024/november/crispr-noncoding-rnas-cell.html
- https://www.cell.com/cell/fulltext/S0092-8674(24)01203-0
トランスクリプトーム規模のRNA標的CRISPRスクリーニングにより、ヒト細胞における必須lncRNAが明らかになる Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells
Wen-Wei Liang∙ Simon Müller∙ Sydney K. Hart∙ … ∙ Olena Kolumba∙ Breanna Williams∙ Neville E. Sanjana
Cell Published:November 11, 2024
DOI:https://doi.org/10.1016/j.cell.2024.10.021
Graphical abstract
Highlights
•Transcriptome-wide CRISPR-Cas13 screens to identify essential human lncRNAs
•Discovery of 46 universally essential and >700 context-specific essential lncRNAs
•Most essential lncRNAs operate independently of their nearest protein-coding genes
•Dynamic expression of essential lncRNAs during development and in specific tumors
Summary
Mammalian genomes host a diverse array of RNA that includes protein-coding and noncoding transcripts. However, the functional roles of most long noncoding RNAs (lncRNAs) remain elusive. Using RNA-targeting CRISPR-Cas13 screens, we probed how the loss of ∼6,200 lncRNAs impacts cell fitness across five human cell lines and identified 778 lncRNAs with context-specific or broad essentiality. We confirm their essentiality with individual perturbations and find that the majority of essential lncRNAs operate independently of their nearest protein-coding genes. Using transcriptome profiling in single cells, we discover that the loss of essential lncRNAs impairs cell-cycle progression and drives apoptosis. Many essential lncRNAs demonstrate dynamic expression across tissues during development. Using ∼9,000 primary tumors, we pinpoint those lncRNAs whose expression in tumors correlates with survival, yielding new biomarkers and potential therapeutic targets. This transcriptome-wide survey of functional lncRNAs advances our understanding of noncoding transcripts and demonstrates the potential of transcriptome-scale noncoding screens with Cas13.
