Yes-associated protein 1 messenger RNA 3' untranslated region (YAP1 mRNA 3'UTR) (YAP1 mRNA 3'UTR)

The Yes-associated protein 1 (YAP1) messenger RNA 3' untranslated region (3'UTR) is a pivotal regulatory domain that controls the expression of the YAP1 protein, a primary effector of the Hippo signaling pathway (Harvey et al., 2013). This region contains multiple conserved binding sites for microRNAs, such as miR-375 and miR-15/16, which post-transcriptionally repress YAP1 to maintain cellular homeostasis (Liu et al., 2010; Piccolo et al., 2014). In various malignancies, including hepatocellular carcinoma and lung cancer, the loss of these inhibitory interactions or the shortening of the 3'UTR leads to YAP1 overexpression, driving tumor growth, metastasis, and resistance to chemotherapy (Moroishi et al., 2015). Consequently, the YAP1 mRNA 3'UTR has emerged as a strategic target for RNA-based therapeutics, such as antisense oligonucleotides and miRNA mimics, designed to restore translational control or trigger mRNA degradation (Crooke et al., 2018). Successfully modulating this target offers a potential pathway to inhibit the oncogenic Hippo-YAP axis, although challenges regarding systemic delivery and the maintenance of normal tissue regenerative capacity must be addressed.

Other names

YAP1 3'UTRYAP 3'UTRYAP1 3'-UTRYes-associated protein 1 3-prime untranslated region

Therapeutic agents targeting the YAP1 mRNA 3'UTR typically utilize antisense oligonucleotides (ASOs) or microRNA (miRNA) mimics to induce sequence-specific degradation of the transcript via RNase H-mediated cleavage or the RNA-induced silencing complex (RISC) (Crooke et al., 2018). Alternatively, agents may sterically block the binding of stabilizing RNA-binding proteins or disrupt secondary structures required for translation, thereby reducing the expression of the YAP1 oncoprotein (Piccolo et al., 2014).