Editors' ChoiceCholesterol

MiR-33 in Cholesterol Control

Science Signaling  22 Jun 2010:
Vol. 3, Issue 127, pp. ec189
DOI: 10.1126/scisignal.3127ec189

With the well-established link between serum cholesterol levels and cardiovascular disease and the availability of effective cholesterol-lowering drugs, cholesterol screening has rapidly become a routine part of health care. Yet, much remains to be learned about how cholesterol levels are regulated at the cellular level (see the Perspective by Brown et al.). Now, Najafi-Shoushtari et al. and Rayner et al. have discovered a new molecular player in cholesterol control—a small noncoding RNA that, intriguingly, is embedded within the genes coding for sterol regulatory element–binding proteins (SREBPs), transcription factors already known to regulate cholesterol levels. This microRNA, called miR-33, represses expression of the adenosine triphosphate–binding cassette transporter A1, a protein that regulates synthesis of high-density lipoprotein (HDL, or “good” cholesterol) and that helps to remove “bad” cholesterol from the blood. Reducing the levels of miR-33 in mice boosted serum HDL levels, suggesting that manipulation of this regulatory circuit might be therapeutically useful.

S. H. Najafi-Shoushtari, F. Kristo, Y. Li, T. Shioda, D. E. Cohen, R. E. Gerszten, A. M. Näär, MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science 328, 1566–1569 (2010). [Abstract] [Full Text]

K. J. Rayner, Y. Suárez, A. Dávalos, S. Parathath, M. L. Fitzgerald, N. Tamehiro, E. A. Fisher, K. J. Moore, C. Fernández-Hernando, MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328, 1570–1573 (2010). [Abstract] [Full Text]

M. S. Brown, J. Ye, J. L. Goldstein, HDL miR-ed down by SREBP introns. Science 328, 1495–1496 (2010). [Summary] [Full Text]