Inhibition of translation initiation by a microRNA

Abstract

Introduction MicroRNAs (miRNAs) are small (∼22 nt) regulatory RNAs that are processed from stem-loop-forming precursor transcripts (Bartel, 2004; He and Hannon, 2004; Meister and Tuschl, 2004). In recent years, they have become the subject of intensive research, which quickly amassed a wealth of information on their biogenesis, function and significance for gene regulation. It also became apparent that miRNAs are an abundant class of gene regulators. The miRBase database (Release 7.1) lists 3424 miRNA sequence entries from various metazoa, plants and some viruses. Entries for intensely studied organisms number in the hundreds of distinct miRNA sequences, many of which exhibit phylogenetic conservation (Griffiths-Jones, 2004). Bioinformatic analyses predict that each miRNA will target multiple mRNAs (Lewis et al., 2003; Bartel, 2004; Lai, 2004; Brennecke et al., 2005; Krek et al., 2005), suggesting that, collectively, these novel gene regulators affect the expression of large portions of the cellular transcriptome. The biological significance of miRNAs is further corroborated by studies of individual examples, reporting their roles in diverse cellular and developmental pathways (see Brennecke et al., 2003; Johnston and Hobert, 2003; Xu et al., 2003; Chen et al., 2004; Zhao et al., 2005). The miRNAs assemble into RNA–protein complexes, usually termed miRNP or RISC (for RNA-induced silencing complex). Different purification schemes have identified a number of resident proteins of miRNP/RISC complexes, with a member of the Argonaute (Ago) protein family consistently found in each preparation (Mourelatos et al., 2002; Dostie et al., 2003; Jin et al., 2004; Chendrimada et al., 2005; Meister et al., 2005). Show more