RNA G-quadruplex (rG4) (rG4)

RNA G-quadruplexes (rG4s) are highly stable, non-canonical secondary structures formed by guanine-rich RNA sequences through Hoogsteen base pairing. These structures are widely distributed across the human transcriptome, particularly within the 5' untranslated regions (UTRs) of mRNAs, where they typically function as steric hurdles that repress translation (Kwok et al., 2017, Trends Biochem Sci). Beyond translation, rG4s play critical roles in regulating alternative splicing, mRNA localization, and the stability of long non-coding RNAs (Fay et al., 2017, J Biol Chem). In oncology, rG4s are often found in the transcripts of key proto-oncogenes, making them attractive targets for small-molecule stabilization to downregulate protein expression (Balasubramanian et al., 2011, Nat Rev Drug Discov). Additionally, expanded G-rich repeats in neurodegenerative diseases, such as those in the C9orf72 gene, form toxic rG4 structures that contribute to disease pathogenesis (Haeusler et al., 2014, Nature). Therapeutic strategies focus on using ligands to stabilize these structures to modulate gene expression or prevent toxic protein aggregation. Recent research also highlights the role of rG4s in viral genomes, such as HIV-1 and SARS-CoV-2, where they regulate viral replication and assembly (Wang et al., 2021, Nucleic Acids Res).

Other names

G-quadruplex-forming RNArG4RNA G4G4-RNA

Small molecule stabilization of rG4 structures to inhibit ribosomal scanning and translation, or to disrupt RNA-protein interactions.