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Abstract

MicroRNAs (miRNAs) are small, ~22-nucleotide-long noncoding RNAs. They silence the expression of messenger RNAs (mRNAs) containing complementary sequences (1). The human genome encodes ~1500 miRNAs, each with the potential to bind hundreds of different mRNAs (1). miRNAs regulate many biological processes, and the dysregulation of their expression is linked to various human diseases, including cancer (1). To exert their repressive function, miRNAs associate with the Argonaute family of proteins (AGOs) to form the core of miRNA-induced silencing complexes (miRISCs) (1) (see the figure). In animals, miRISCs silence mRNA expression at two levels, by preventing protein production (translation) and inducing mRNA degradation. Over the past decade, progress has been made in our understanding of the mechanism by which miRISCs induce mRNA degradation, but the question of how miRISCs repress translation remains elusive.