Carnitine O-octanoyltransferase mRNA 3'-untranslated region (CROT mRNA 3'-UTR)

The Carnitine O-octanoyltransferase (CROT) mRNA 3'-untranslated region (3'-UTR) is a critical regulatory segment of the CROT transcript that controls the expression of the CROT enzyme. CROT is a peroxisomal enzyme essential for the transport of medium- and long-chain acyl-CoA esters out of peroxisomes for further oxidation in mitochondria (Davalos et al., J Lipid Res, 2011). The 3'-UTR of CROT contains highly conserved binding sites for microRNA-33 (miR-33), which post-transcriptionally represses CROT expression, thereby inhibiting fatty acid oxidation and contributing to lipid accumulation. In the context of drug development, the CROT mRNA 3'-UTR is a focal point for treating metabolic and cardiovascular diseases. By utilizing miR-33 inhibitors such as Lademirsen (RG-125), researchers aim to block the interaction between the microRNA and the CROT 3'-UTR, effectively de-repressing the gene to enhance lipid catabolism. This strategy is primarily investigated for its potential to reduce hepatic steatosis in nonalcoholic fatty liver disease and to improve lipid profiles in patients with atherosclerosis (Moore et al., Nature, 2013; Rayner et al., Science, 2010).

Other names

CROT 3'-UTRCarnitine octanoyltransferase 3'-untranslated regionCROT 3'-untranslated region

The CROT mRNA 3'-untranslated region serves as a binding site for microRNA-33 (miR-33a/b). Therapeutic intervention typically involves using antisense oligonucleotides (antagomirs) to bind and sequester miR-33, thereby preventing it from interacting with the CROT 3'-UTR. This inhibition prevents the degradation of CROT mRNA and the repression of its translation, leading to increased levels of the Carnitine O-octanoyltransferase enzyme and a subsequent increase in peroxisomal fatty acid oxidation (Rayner et al., Science, 2010; Davalos et al., J Lipid Res, 2011).