Post-transcriptional control of KRAS: functional roles of 5'UTR RNA G-quadruplexes, long noncoding RNA, and hnRNPA1.

ABSTRACT: Previous studies have shown that human KRAS expression is regulated at the transcriptional level by G-quadruplex DNA structures within its promoter. Here we show an additional level of regulation involving a post-transcriptional mechanism centred on the 5'-untranslated region (5'UTR) of the messenger RNA (mRNA) characterized by G4 structures (rG4s). Long noncoding RNAs (lncRNAs) and the protein hnRNPA1 are also involved in this mechanism. RIP-seq confirmed the presence of rG4s in the 5'UTR. Deletion of the rG4 region using CRISPR/Cas9 resulted in a significant increase in KRAS mRNA levels, indicating the role of the 5'UTR in controlling mRNA levels. RIP shows that hnRNPA1 is recruited to the 5'UTR, where it unfolds the rG4 structures and potentially affects mRNA stability. In addition, lnc

SUBMITTER: Cortolezzis Y 

PROVIDER: S-EPMC12449053 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature