Cullin 4A messenger RNA 3' untranslated region (CUL4A mRNA 3'UTR) (CUL4A mRNA 3'UTR)

Cullin 4A (CUL4A) is a scaffold protein that forms part of the Cullin-RING ubiquitin ligase (CRL4) complex, which is essential for the ubiquitination and subsequent degradation of various regulatory proteins involved in DNA replication, repair, and cell cycle progression (UniProt P39905). The 3' untranslated region (3'UTR) of the CUL4A mRNA serves as a critical regulatory hub, containing multiple binding sites for microRNAs (miRNAs) such as miR-124, miR-194, and miR-494, which normally suppress CUL4A expression (PubMed: 25605130, 26823714, 25193394). In many cancers, CUL4A is overexpressed due to the downregulation of these inhibitory miRNAs or genomic amplification, leading to the accelerated degradation of tumor suppressors like p53 and p21 (PubMed: 23835303). Consequently, the CUL4A mRNA 3'UTR is an attractive therapeutic target for RNA-based interventions, including miRNA mimics or antisense oligonucleotides, designed to restore post-transcriptional silencing and reduce oncogenic CUL4A levels. Modulating this region has shown potential in preclinical models to inhibit tumor cell proliferation, invasion, and epithelial-mesenchymal transition. This target represents a specific site for precision medicine approaches aimed at correcting the dysregulated protein degradation pathways characteristic of aggressive malignancies.

Other names

CUL4A 3'UTRCullin-4A 3' untranslated regionCUL4A mRNA 3-prime untranslated regionCUL4A 3-prime UTR

Binding of microRNA mimics or antisense oligonucleotides to the 3'UTR sequence induces mRNA degradation or inhibits translation, thereby reducing the cellular levels of the oncogenic CUL4A protein.