Kirsten rat sarcoma virus oncogene homolog messenger RNA G-quadruplex in the 5'-untranslated region (KRAS 5'-UTR G4)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) mRNA G-quadruplex in the 5'-untranslated region (5'-UTR) is a complex four-stranded secondary structure formed by guanine-rich sequences (Cogoi et al., 2010, J Biol Chem). This structural element serves as a critical regulatory node in the post-transcriptional control of KRAS expression, a protein that functions as a molecular switch in signaling pathways governing cell growth and survival. In the context of oncology, KRAS is one of the most frequently mutated oncogenes, particularly in pancreatic, colorectal, and lung cancers, where it drives aggressive tumor progression (Xodo et al., 2016, Expert Opin Ther Targets). Therapeutic strategies targeting this G-quadruplex involve the use of small-molecule ligands, such as naphthalene diimide derivatives, that bind and stabilize the structure (Cogoi et al., 2014, Nucleic Acids Res). This stabilization creates a steric hindrance that prevents the 40S ribosomal subunit from scanning the mRNA, effectively silencing the translation of the KRAS oncogene. This approach provides a mutation-agnostic strategy to inhibit KRAS signaling, potentially addressing a wide range of KRAS-driven malignancies that are otherwise difficult to treat.

Other names

KRAS mRNA G-quadruplexKRAS 5'-UTR G-quadruplexKRAS G4 structure

Stabilization of the G-quadruplex structure within the 5'-untranslated region of KRAS mRNA to sterically inhibit ribosomal scanning and subsequent protein translation (Cogoi et al., 2010, J Biol Chem; Xodo et al., 2016, Expert Opin Ther Targets).