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Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
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RETRACTED: Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells
Wen-Wei Liang1, Simon Müller1, Sydney K Hart1
1New York Genome Center, New York, NY 10013, USA; Department of Biology, New York University, New York, NY 10013, USA.
Cell
|November 12, 2024
Summary
Researchers identified 778 essential long noncoding RNAs (lncRNAs) impacting cell fitness using CRISPR-Cas13 screens. These functional lncRNAs offer new insights into noncoding RNA roles and potential cancer biomarkers.
Area of Science:
- Genomics
- Molecular Biology
- RNA Biology
Background:
- Mammalian genomes contain numerous protein-coding and noncoding transcripts.
- The functions of most long noncoding RNAs (lncRNAs) are not well understood.
- Understanding lncRNA function is crucial for advancing molecular biology.
Purpose of the Study:
- To systematically identify essential long noncoding RNAs (lncRNAs) across diverse human cell lines.
- To investigate the functional impact of lncRNA loss on cell fitness and biological processes.
- To discover novel lncRNA biomarkers and therapeutic targets in cancer.
Main Methods:
- Utilized RNA-targeting CRISPR-Cas13 screening to assess the impact of deleting ~6,200 lncRNAs on cell fitness.
- Performed individual gene perturbations to validate essential lncRNAs.
- Conducted single-cell transcriptome profiling to analyze cellular responses to lncRNA loss.
- Analyzed gene expression data from ~9,000 primary tumors to identify survival-associated lncRNAs.
Main Results:
- Identified 778 essential lncRNAs with context-specific or broad essentiality across five human cell lines.
- Demonstrated that most essential lncRNAs function independently of neighboring protein-coding genes.
- Found that loss of essential lncRNAs disrupts cell-cycle progression and induces apoptosis.
- Discovered dynamic expression patterns of essential lncRNAs during development.
- Identified lncRNAs whose tumor expression correlates with patient survival, indicating potential biomarkers and therapeutic targets.
Conclusions:
- This study presents a comprehensive functional survey of lncRNAs, identifying a significant number of essential ones.
- The findings highlight the critical roles of lncRNAs in fundamental cellular processes like cell-cycle regulation and apoptosis.
- The identified lncRNAs represent promising candidates for cancer biomarker development and therapeutic intervention.
- Demonstrated the power of CRISPR-Cas13-based transcriptome-wide screens for functional noncoding RNA research.
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