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Three-dimensional genome organization via triplex-forming RNAs
Nature Structural & Molecular Biology ( IF 16.8 ) Pub Date : 2021-11-10 , DOI: 10.1038/s41594-021-00678-3
Irene Farabella 1 , Marco Di Stefano 1, 2 , Paula Soler-Vila 1, 3 , Maria Marti-Marimon 1 , Marc A Marti-Renom 1, 4, 5, 6
Affiliation  

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.



中文翻译:

通过形成三链体的 RNA 进行三维基因组组织

越来越多的长链非编码 RNA (lncRNA) 被提议在间期充当核组织因子。直接的 RNA-DNA 相互作用可以通过形成三螺旋结构来实现,其中单链 RNA 分子通过互补性杂交到双链 DNA 的大沟中。然而,这些直接的 RNA-DNA 关联是否以及如何影响间期染色体的基因组结构仍然知之甚少。在这里,我们推测 RNA 通过三链体形成机制在空间中组织基因组。为了检验这一理论,我们应用了一种染色体计算建模方法,该方法将基于约束的建模与聚合物物理学相结合。我们的模型表明,lncRNA 靶向的三重热点的共定位可能有助于大规模染色体区室化合作,

更新日期:2021-11-10
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