Kirsten rat sarcoma virus oncogene homolog mRNA 3'-untranslated region (KRAS mRNA 3'-UTR)

The Kirsten rat sarcoma virus oncogene homolog (KRAS) mRNA 3'-untranslated region (3'-UTR) is an extensive regulatory sequence, approximately 4.5 kilobases in length, that plays a pivotal role in the post-transcriptional control of the KRAS oncogene. It contains a multitude of cis-acting elements, including binding sites for microRNAs (miRNAs) such as the let-7 family and miR-185, as well as various RNA-binding proteins like HuR and AGO2. These interactions are essential for maintaining appropriate KRAS expression levels by regulating mRNA stability and translation. Genetic variations within this region, such as the rs61764370 single nucleotide polymorphism (SNP), can disrupt miRNA-mediated repression, leading to elevated KRAS protein levels and increased susceptibility to various cancers, including lung, colorectal, and pancreatic adenocarcinomas. Consequently, the KRAS mRNA 3'-UTR has emerged as a significant therapeutic target for RNA-based strategies, including miRNA mimics and antisense oligonucleotides (ASOs), designed to silence the oncogene or restore regulatory balance. By targeting the mRNA regulatory machinery, these approaches aim to overcome the historical challenges associated with directly inhibiting the KRAS protein.

Other names

KRAS 3'-UTRKRAS 3' untranslated regionKRAS mRNA 3' regulatory regionKRAS 3'-UTR cis-regulatory elementsKirsten rat sarcoma virus oncogene homolog 3'-UTR

RNA interference (RNAi), RNase H-mediated mRNA degradation, translational repression, and competitive inhibition of microRNA binding sites.