RNA-DNA Triplex Formation by Long Noncoding RNAs

Long noncoding RNAs (lncRNAs) play a pivotal role in the regulation of biological processes through various mechanisms that are not fully understood. Proposed mechanisms include regulation based on RNA-protein interactions, as well as RNA-RNA interactions and RNA-DNA interactions. Here, researchers from Kyoto University focus on one possible mechanism that lncRNA might be using to impact biological function, the RNA-DNA triplex formation. They summarize currently available examples of lncRNA triplex formation and discuss the details surrounding orientation of triplex formation as one of the key properties guiding this process. They propose that symmetrical triplex-forming motifs, especially those in cis-acting lncRNAs, favor triplex formation. The authors also consider the effects of lncRNA structures, protein or ligand binding, and chromatin structures on the lncRNAs triplex formation.

Triplex Formation between the Third-Strand Oligonucleotide and dsDNA


(A) Examples of Hoogsteen and reverse Hoogsteen hydrogen bonding in the triplex formation.

(B) Illustration of parallel and antiparallel triplex formation. The arrow indicates 5′ to 3′ direction.

(C) Structure of RNA-DNA triplex. The third-strand RNA (brown) binds to the major groove of the DNA duplex. The picture was generated by the reported RNA-DNA triplex structure (PDB: 1R3X) (Gotfredsen et al., 1998).

Li Y, Syed J, Sugiyama H. (2016) RNA-DNA Triplex Formation by Long Noncoding RNAs. Cell Chem Biol [Epub ahead of print]. [abstract]

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