Autophagy-related protein 12 messenger RNA 3' untranslated region (ATG12 mRNA 3'UTR)

The Autophagy-related protein 12 (ATG12) mRNA 3' untranslated region (3'UTR) is a key regulatory sequence that controls the expression of the ATG12 protein, a vital component of the autophagy machinery. ATG12 functions by forming a covalent conjugate with ATG5, which then complexes with ATG16L1 to facilitate the lipidation of LC3, a process essential for autophagosome membrane elongation (Mizushima et al., 1998; UniProt Q9H120). The 3'UTR of ATG12 is a frequent target for various microRNAs (miRNAs), such as miR-21, miR-30e-5p, and miR-214, which act as post-transcriptional repressors by binding to specific seed sequences (PubMed 31031943; NIH Gene ID: 9140). Dysregulation of this regulatory axis is implicated in numerous diseases, including various cancers where it influences chemoresistance and cell survival, as well as cardiovascular diseases like myocardial infarction. In oncological contexts, the 3'UTR often serves as a site for 'sponging' by long non-coding RNAs (lncRNAs), which prevents miRNAs from binding and leads to ATG12 overexpression and excessive autophagy. Consequently, the ATG12 mRNA 3'UTR is being explored as a therapeutic target for RNA-based drugs, including miRNA mimics and antisense oligonucleotides, to modulate autophagic flux for clinical benefit. Research indicates that targeting this region can sensitize cancer cells to chemotherapy by inhibiting protective autophagy or inducing apoptosis through ATG12's interaction with Bcl-2 family members (PubMed 21623370).

Other names

ATG12 3'UTRAutophagy-related 12 3'UTRAPG12 mRNA 3'UTRATG12 3-prime untranslated region

MicroRNAs or other RNA-targeting agents bind to the 3'UTR sequence of ATG12 mRNA, leading to its degradation or the inhibition of its translation, which reduces ATG12 protein levels and suppresses autophagosome formation.