Abstract
Over the last decades, numerous examples have involved nuclear non-coding RNAs (ncRNAs) in the regulation of gene expression. ncRNAs can interact with the genome by forming non-canonical nucleic acid structures such as R-loops or DNA:RNA triplexes. They bind chromatin and DNA modifiers and transcription factors and favor or prevent their targeting to specific DNA sequences and regulate gene expression of diverse genes. We review the function of these non-canonical nucleic acid structures in regulating gene expression of multicellular organisms during development and in response to different stress conditions and DNA damage using examples described in several organisms, from plants to humans. We also overview recent techniques developed to study where R-loops or DNA:RNA triplexes are formed in the genome and their interaction with proteins.
Highlights
Non-canonical nucleic acid structures involving RNA can adopt different forms like R-loops and DNA:RNA triplexes and differ structurally from double-stranded DNA by adopting a non-B-form (Wang et al, 1982; Radhakrishnan and Patel 1994)
Samples are treated with a commercial RNase H for 30 min, which is insufficient to remove all RNA-DNA hybrids; a fraction of the RNA-DNA hybrids, the main part of R-loops, might still be present and identified as DNA:RNA triplexes (Alecki and Francis 2021). They observed that 20% of the peaks of their putative DNA:RNA triplexes overlapped with previously published R-loop forming sequences, suggesting that these RNAs tend to form different non-canonical nucleic acid structures or that their protocol is not fully specific for the identification of DNA:RNA triplexes in vivo
R-loop dependent targeting of translocation methylcytosine dioxygenase 1 (TET1) is not restricted to the TCF21 gene because the overexpression of RNase H1, enzyme degrading the RNA moiety of an RNA-DNA hybrid, leads to a decreased binding of GADD45 alpha (GADD45A) and TET1 at other binding sites controlling the expression of transcriptional coactivators and repressors, and chromatin binding proteins
Summary
Non-canonical nucleic acid structures involving RNA can adopt different forms like R-loops and DNA:RNA triplexes and differ structurally from double-stranded DNA (dsDNA) by adopting a non-B-form (Wang et al, 1982; Radhakrishnan and Patel 1994). We discuss studies demonstrating that noncanonical nucleic acid structures act to provide sequence specificity to epigenetic and DNA modifications and transcription factors They participate in the target of epigenetic modifiers, like the Polycomb complex PRC2, which lack sequence-specific binding activity, to specific regions of the genome and can prevent the targeting of others (Alecki et al, 2020; Skourti-Stathaki et al, 2019; Arab et al, 2019; Grote et al, 2013; Schmitz et al, 2010; Postepska-Igielska et al, 2015; Cristini et al, 2018; Wang et al, 2018). We review the principles and advantages that these techniques offer to non-canonical nucleic acid structures
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