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(Circulation. 2009;119:2217-2224.)
© 2009 American Heart Association, Inc.

Basic Science for Clinicians

MicroRNAs

Regulating a Change of Heart

Kurt G. Barringhaus, MD; Phillip D. Zamore, PhD

From the Department of Cardiovascular Medicine (K.G.B.) and the Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology (P.D.Z.), University of Massachusetts Medical School, Worcester.

Correspondence to Kurt G. Barringhaus or Phillip D. Zamore, University of Massachusetts Medical School, LRB 821, 364 Plantation St, Worcester, MA 01605. E-mail kurt.barringhaus@umassmed.edu or phillip.zamore@umassmed.edu

Key Words: cardiovascular diseases • genes • microRNA • molecular biology • myocardium

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
MicroRNAs (miRNAs) are small RNAs, 22 nucleotides long, that direct proteins to repress expression of mRNAs with which they are partially complementary. miRNAs are 1 of several classes of small RNA guides that provide sequence specificity to RNA silencing pathways (reviewed in Ghildiyal and Zamore¹). In many respects, miRNAs are the normal cellular counterparts to small interfering RNAs (siRNAs), which guide RNA interference (RNAi), arguably the most famous RNA silencing pathway. With the exception of some ubiquitously expressed housekeeping genes, nearly every animal mRNA may, at some time in development and in 1 or more cell types, be repressed by 1 or more miRNAs. Thus, it is not surprising that miRNAs regulate key genetic programs in cardiovascular biology and are critical for cardiac development, endothelial function, lipid metabolism, ventricular hypertrophy, and postinfarction dysrhythmias. In this review, we first define the key components of the RNA silencing pathway and then examine how RNA silencing regulates cardiovascular biology. Finally, we explore the opportunities miRNAs may provide for therapeutic intervention in human cardiac disease.

	History and Mechanism

 
RNA silencing was first observed in plants^2,3 and later in animals.^4,5 The first miRNA was identified by Ambros and colleagues⁶ in the nematode Caenorhabditis elegans in 1993, 6 years before the discovery of siRNAs.⁷ The discovery of a second nematode miRNA, let-7,⁸ allowed the identification of its homologs in other animals, including humans,⁹ and additional miRNAs were soon identified in flies, worms, and humans by direct sequencing of small RNAs.^10–12 Like the original nematode miRNAs, lin-4 and . . . [Full Text of this Article]

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