Three-dimensional genome organization via triplex-forming RNAs

Farabella, Irene; Di Stefano, Marco; Soler-Vila, Paula; Marti Marimon, Maria; Marti-Renom, Marc A.

doi:http://dx.doi.org/10.1038/s41594-021-00678-3

Three-dimensional genome organization via triplex-forming RNAs

Citation

Farabella I, Di Stefano M, Soler-Vila P, Marti-Marimon M, Marti-Renom MA. Three-dimensional genome organization via triplex-forming RNAs. Nat Struct Mol Biol. 2021 Nov;28(11):945-954. DOI: 10.1038/s41594-021-00678-3

Abstract

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.