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

## TL;DR

This review explores how RNA–DNA interactions regulate key cellular processes and their roles in health and disease.

## Contribution

The paper provides a comprehensive overview of RNA–DNA hybrid structures and their physiological roles.

## Key findings

- R-loops regulate gene expression but can threaten genome stability.
- RNA–DNA triplexes modulate gene expression through chromatin modifiers like Polycomb repressive complex 2.
- hG4s influence transcription termination and telomere stability, impacting gene suppression and replication.

## Abstract

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.