Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?

Abstract

MicroRNAs (miRNAs) — approximately 21-nucleotide-long, genome-encoded RNAs — have emerged as key regulators of gene expression in eukaryotes. miRNAs represent just one class of small RNA regulators, the others being small interfering RNAs (siRNAs) and PIWI-associated RNAs (piRNAs), all of which operate in processes that are collectively referred to as RNA silencing. miRNAs control gene expression post-transcriptionallly, by hybridizing to target mRNAs and thereby regulating their translation or stability. By targeting dozens or even hundreds of different mRNAs, individual miRNAs have the potential to fine-tune or modulate the expression of genes that participate in a specific metabolic or developmental pathway; but they can also act as reversible switches to turn on and off mRNA translation. miRNAs function as components of ribonucleoprotein (RNP) complexes, referred to as either miRNPs or miRNA-induced silencing complexes (miRISCs), with proteins of the Argonaute (AGO) family being the most important and best characterized components. Studies performed both in vivo and in cell-free extracts have provided some mechanistic insights into the miRNA-mediated repression, although many details of the repression are still poorly understood.