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J Lipid Res. 2014 Apr 11;55(6):1066-1076. [Epub ahead of print]

RNA binding protein HuR regulates the expression of ABCA1.

Author information

  • 1Vascular Biology and Therapeutics Program, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520 Departments of Medicine and Cell Biology, New York University School of Medicine, New York, NY 10016.
  • 2Departments of Medicine and Cell Biology, New York University School of Medicine, New York, NY 10016 Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
  • 3Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
  • 4Departments of Medicine and Cell Biology, New York University School of Medicine, New York, NY 10016.
  • 5Vascular Research Lab, IIS-Fundación Jimenez Díaz, Autónoma University, Madrid 28040, Spain.
  • 6Children's Cancer Research Institute, Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229.
  • 7Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089.

Abstract

ABCA1 is a major regulator of cellular cholesterol efflux and plasma HDL biogenesis. Even though the transcriptional activation of ABCA1 is well established, the posttranscriptional regulation of ABCA1 expression is poorly understood. Here, we investigate the potential contribution of the RNA binding protein (RBP) human antigen R (HuR) on the posttranscriptional regulation of ABCA1 expression. RNA immunoprecipitation assays demonstrate a direct interaction between HuR and ABCA1 mRNA. We found that HuR binds to the 3' untranslated region of ABCA1 and increases ABCA1 translation, while HuR silencing reduces ABCA1 expression and cholesterol efflux to ApoA1 in human hepatic (Huh-7) and monocytic (THP-1) cells. Interestingly, cellular cholesterol levels regulate the expression, intracellular localization, and interaction between HuR and ABCA1 mRNA. Finally, we found that HuR expression was significantly increased in macrophages from human atherosclerotic plaques, suggesting an important role for this RBP in controlling macrophage cholesterol metabolism in vivo. In summary, we have identified HuR as a novel posttranscriptional regulator of ABCA1 expression and cellular cholesterol homeostasis, thereby opening new avenues for increasing cholesterol efflux from atherosclerotic foam macrophages and raising circulat-ing HDL cholesterol levels.

KEYWORDS:

ATP binding cassette transporter A1; cholesterol efflux; human antigen R; lipid homeostasis; posttranscriptional regulation

PMID:
24729624
[PubMed - as supplied by publisher]
PMCID:
PMC4031938
[Available on 2015-06-01]
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