Three-dimensional genome organization via triplex-forming RNAs
I Farabella and M Di Stefano and P Soler-Vila and M Marti-Marimon and MA Marti-Renom, NATURE STRUCTURAL & MOLECULAR BIOLOGY, 28, 945-+ (2021).
An increasing number of long noncoding RNAs (lncRNAs) have been proposed to act as nuclear organization factors during interphase. Direct RNA-DNA interactions can be achieved by the formation of triplex helix structures where a single-stranded RNA molecule hybridizes by complementarity into the major groove of double-stranded DNA. However, whether and how these direct RNA-DNA associations influence genome structure in interphase chromosomes remain poorly understood. Here we theorize that RNA organizes the genome in space via a triplex-forming mechanism. To test this theory, we apply a computational modeling approach of chromosomes that combines restraint-based modeling with polymer physics. Our models suggest that colocalization of triplex hotspots targeted by lncRNAs could contribute to large-scale chromosome compartmentalization cooperating, rather than competing, with architectural transcription factors such as CTCF. Here the authors computationally test the hypothesis that RNA organizes the three- dimensional genome via a triplex-forming mechanism, providing evidence that lncRNA-targeted triplex hotspots can contribute to large-scale chromosome compartmentalization.
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