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Three-dimensional genome organization via triplex-forming RNAs.
Irene Farabella1, Marco Di Stefano2,3, Paula Soler-Vila2,4
1CNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain. irene.farabella@cnag.crg.eu.
Nature Structural & Molecular Biology
|November 11, 2021
Summary
Long noncoding RNAs (lncRNAs) may organize genome structure by forming direct RNA-DNA triplexes. This mechanism could contribute to chromosome compartmentalization, working alongside proteins like CTCF.
Area of Science:
- Genomics
- Molecular Biology
- Biophysics
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized as nuclear organization factors.
- Direct RNA-DNA interactions via triplex formation are possible but their role in genome structure is unclear.
Purpose of the Study:
- To investigate the role of RNA in organizing genome structure during interphase.
- To test the theory that RNA organizes the genome via a triplex-forming mechanism.
Main Methods:
- Utilized computational modeling of chromosomes.
- Combined restraint-based modeling with polymer physics principles.
Main Results:
- Models suggest RNA-DNA triplex formation is a viable mechanism for genome organization.
- Colocalization of lncRNA-targeted triplex hotspots may drive large-scale chromosome compartmentalization.
Conclusions:
- RNA, through triplex formation, can act as a genome organizer.
- This RNA-mediated organization likely cooperates with known architectural factors like CTCF.
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