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ATP-binding cassette transporter A1 mRNA 3'-untranslated region (ABCA1 mRNA 3'-UTR) (ABCA1 mRNA 3'-UTR)

Target
ABCA1 mRNA 3'-UTR
Molecular classification
Nucleic acid, mRNA regulatory region
01

Overview

The ATP-binding cassette transporter A1 (ABCA1) mRNA 3'-untranslated region (3'-UTR) is a key regulatory element that governs the post-transcriptional expression of the ABCA1 protein (UniProt: P94187). ABCA1 plays a fundamental role in cellular lipid homeostasis by facilitating the efflux of cholesterol and phospholipids to apolipoprotein A-I (apoA-I), which is the rate-limiting step in the biogenesis of high-density lipoprotein (HDL) particles. The 3'-UTR of ABCA1 is notably long and contains conserved binding sites for several microRNAs, most significantly miR-33a/b, which act to suppress ABCA1 translation and promote mRNA decay (Rayner et al., Science, 2010; PMID: 20466885). Therapeutic strategies targeting this region involve using antisense oligonucleotides or microRNA inhibitors to block these inhibitory interactions, thereby increasing ABCA1 protein levels (Rotllan et al., J Lipid Res, 2016; PMID: 26839344). Upregulation of ABCA1 via its 3'-UTR is a major area of research for treating atherosclerosis, as it promotes reverse cholesterol transport and reduces the formation of foam cells in arterial walls. Additionally, this target is being investigated for its potential role in neurodegenerative diseases like Alzheimer's, where ABCA1-mediated lipid transport influences amyloid-beta clearance (Koldamova et al., J Biol Chem, 2014; PMID: 24610481).

Other names
ABCA1 3'-UTRATP-binding cassette sub-family A member 1 mRNA 3'-untranslated regionCholesterol efflux regulatory protein mRNA 3'-UTR
02

Mechanism of action

Inhibition of microRNA binding (specifically miR-33) to the 3'-UTR to prevent translational repression and mRNA degradation, leading to increased ABCA1 protein expression and enhanced cholesterol efflux (Rayner et al., Science, 2010; PMID: 20466885).

03

Biological functions

Regulation of mRNA stabilityRegulation of translationCholesterol efflux regulationLipid homeostasis
04

Disease associations

Cardiovascular diseaseAtherosclerosisTangier diseaseMetabolic syndromeAlzheimer's disease
05

Safety considerations

Off-target effects of antisense oligonucleotidesPotential liver toxicityAlterations in systemic lipid metabolismPotential effects on glucose metabolism and fatty acid oxidation (Moore et al., J Clin Invest, 2013; PMID: 24091323)
06

Interacting drugs

miR-33 inhibitors

3 more in the full profile.

07

Biomarkers

HDL-cholesterol levelsABCA1 protein expressionCholesterol efflux capacityPlasma miR-33 levels

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