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<p>RNA–DNA interactions are fundamental to cellular physiology, playing critical roles in genome integrity, gene expression, and stress responses. This review highlights the diverse structures of RNA–DNA hybrids, including R-loops, RNA–DNA triplexes, and RNA–DNA hybrid G-quadruplexes (hG4s) and their relevance in physiology. R-loops are formed during transcription and replication, which regulate gene expression and chromatin dynamics but can also threaten genome stability. RNA–DNA triplexes, often formed by long noncoding RNAs (lncRNAs) such as <i>FENDRR</i> and <i>MEG3</i>, recruit chromatin modifiers like Polycomb repressive complex 2 to modulate gene expression, influencing organogenesis and cell specification. hG4s, formed by guanine-rich sequences in RNA and DNA, regulate transcription termination and telomere stability. Through this, hG4s can affect gene suppression and replication regulation. RNA–DNA hybrids are tightly regulated by helicases, RNase H enzymes, and topoisomerases, with altered regulation linked to genomic instability and disease. This review discusses the complexity of RNA–DNA interactions and their recently identified contributions to cellular physiology.</p>

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The relevance of RNA–DNA interactions as regulators of physiological functions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月21日

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  • Julia Stötzel,
  • Timothy Warwick,
  • Praveenya Tirunagari,
  • Ralf P. Brandes,
  • Matthias S. Leisegang

摘要

RNA–DNA interactions are fundamental to cellular physiology, playing critical roles in genome integrity, gene expression, and stress responses. This review highlights the diverse structures of RNA–DNA hybrids, including R-loops, RNA–DNA triplexes, and RNA–DNA hybrid G-quadruplexes (hG4s) and their relevance in physiology. R-loops are formed during transcription and replication, which regulate gene expression and chromatin dynamics but can also threaten genome stability. RNA–DNA triplexes, often formed by long noncoding RNAs (lncRNAs) such as FENDRR and MEG3, recruit chromatin modifiers like Polycomb repressive complex 2 to modulate gene expression, influencing organogenesis and cell specification. hG4s, formed by guanine-rich sequences in RNA and DNA, regulate transcription termination and telomere stability. Through this, hG4s can affect gene suppression and replication regulation. RNA–DNA hybrids are tightly regulated by helicases, RNase H enzymes, and topoisomerases, with altered regulation linked to genomic instability and disease. This review discusses the complexity of RNA–DNA interactions and their recently identified contributions to cellular physiology.