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(Circulation. 2008;118:1524-1527.)
© 2008 American Heart Association, Inc.

Editorial

Cardiac Dissonance Without Conductors

How Dicer Depletion Provokes Chaos in the Heart

Thomas Thum, MD, PhD

From the Department of Internal Medicine I, Junior Research Group Cardiac Wounding and Healing, Interdisciplinary Center for Clinical Research (IZKF), University Hospital, Julius Maximilians University, Würzburg, Germany.

Correspondence to Thomas Thum, MD, PhD, Medizinische Klinik und Poliklinik I, Universitätsklinikum, Julius Maximilians Universität, Josef Schneider Straße 2, D-97080, Würzburg, Germany. E-mail Thum_T@klinik.uni-wuerzburg.de

Key Words: Editorials • remodeling • Dicer protein • heart failure • microRNAs

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

Dicer was initially identified as the protein responsible for processing double-stranded RNA into small interference RNAs.¹ Later, it was shown that on interaction with cofactors,² Dicer also produces other kinds of small RNAs, ie, microRNAs (miRNAs).³ MiRNAs are endogenous small ribonucleotides that act as negative regulators of target messenger RNAs. It has been estimated that the human genome encodes up to 1000 miRNAs that modulate 30% to 50% of all genes, which demonstrates the importance of these small regulators as fundamental orchestrators of the genome.

Article p 1567

Primary transcripts (pri-miRNA) are processed in the nucleus into hairpin RNAs by the RNase III–type enzyme Drosha⁴ and the double-stranded RNA binding protein DGCR8⁵ to form pre-miRNAs. On nuclear export, pre-miRNAs are processed by the ribonuclease Dicer into 19- to 25-nucleotide miRNA duplexes, of which 1 strand is implemented into the RNA-induced silencing complex, which then binds to target mRNAs with subsequent mRNA degradation or translational inhibition.⁶ Recent data obtained by performance of parallel transcriptome and proteomic analysis in cells transfected with different miRNAs propose that in mammals, miRNAs exert stronger effects on protein expression than on mRNA levels.⁷ The biological importance of Dicer-mediated maturation of miRNAs has been shown for various cell types, including embryonic stem cells⁸ and germline cells,⁹ as well as for more specialized cell types, such as pancreatic islet cells,¹⁰ immune cells,¹¹ neural cells,¹² or endothelial cells.¹³

A first role for Dicer in cardiac development was described previously. To assess the global requirement for miRNAs in the mouse . . . [Full Text of this Article]