1. ¹Division of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA
2. ²Interagon AS, Trondheim, Norway
3. ³Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Correspondence: John J. Rossi, Division of Molecular Biology, Beckman research Institute of the City of Hope, 1450 E. Duarte Road, Duarte, California 91010, USA. E-mail: jrossi@coh.org

Received 3 July 2007; Accepted 15 August 2007; Published online 18 September 2007.

Abstract

MicroRNAs (miRNAs) are 21–24 nucleotide (nt) duplex RNAs that are created from precursor transcripts by subsequent processing steps mediated by members of the RNAseIII family, Drosha and Dicer. One of the two strands is incorporated into the active sites of the Argonaute family of proteins, where it serves as a guide for Watson–Crick base pairing with complementary sequences in target messenger RNAs (mRNAs). In mammals, the majority of miRNAs guide the RNA-induced silencing complex (RISC) to the 3' untranslated regions (UTRs) of mRNA targets, with the consequence that translation of the target mRNAs is inhibited. The importance of miRNAs in normal cellular development and metabolism is only now being realized. miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from myocardial infarction to cancers. The loss or gain of miRNA function can be caused by a single point mutation in either the miRNA or its target or by epigenetic silencing of primary miRNA transcription units. This review summarizes miRNA biogenesis and biology, explores the potential roles miRNAs can play in a variety of diseases, and suggests some therapeutic applications for restoring or inhibiting miRNA function.