RAS family mRNA 3' untranslated regions (RAS 3'UTRs)

The RAS family mRNA 3' untranslated regions (3'UTRs) are non-coding segments of messenger RNA located downstream of the stop codon in KRAS, HRAS, and NRAS transcripts. These regions serve as critical regulatory hubs, containing binding sites for microRNAs (such as the let-7 family) and various RNA-binding proteins that dictate the stability, localization, and translation efficiency of RAS mRNAs (Johnson et al., 2005, Cell). In many cancers, alterations in these 3'UTRs—such as shortening through alternative polyadenylation or mutations in miRNA binding sites—lead to the evasion of post-transcriptional repression, resulting in the pathological overexpression of RAS proteins (Mayr & Bartel, 2009, Science). Consequently, these regions are being explored as therapeutic targets for RNA-based modalities, including antisense oligonucleotides and miRNA mimics, which aim to restore normal regulatory control or induce the degradation of oncogenic RAS transcripts. Targeting the 3'UTR offers a strategy to modulate RAS levels indirectly, potentially overcoming some of the challenges associated with directly inhibiting the "undruggable" RAS protein surfaces.

Other names

RAS 3'-untranslated regionsKRAS 3'UTRNRAS 3'UTRHRAS 3'UTRRAS mRNA regulatory regions

Modulation of mRNA stability and translation through RNA interference, antisense-mediated degradation, or competitive inhibition of regulatory protein/miRNA binding (Ross et al., 2017, Cancer Cell; Esquela-Kerscher & Slack, 2006, Nat Rev Cancer).