Abstract
Post-transcriptional regulation of gene expression plays important roles in diverse cellular processes such as development, neurogenesis and cancer progression. This regulation is often mediated by specific RNA-binding proteins (RBPs) that bind to elements in the untranslated regions (UTRs) of mRNAs and regulate the stability, translation, or localization of the mRNA. Whereas many classical studies explored the cellular role of RBPs with specific mRNA substrates, the recent development of genome-wide analysis tools enables systematic identification of the mRNA substrates of RBPs, and the study of post-transcriptional gene regulation on a global scale. For instance, mRNAs targeted by specific RBPs can be identified by combining biochemical purification of RBPs followed by the analysis of associated RNAs with DNA microarrays. As exemplified for the Pumilio-Fem-3-binding factor (PUF) proteins, for which the mRNA targets have been systematically identified in yeast and Drosophila, the groups of RNAs associated with RBPs often encode functionally or cytotopically related proteins which act in the same biochemical pathway, are parts of a macromolecular complex or localize to the same subcellular structure. Moreover, the global approach enabled the discovery of conserved sequence elements in the RNA which specify protein binding. These studies suggest extensive coordinate regulation of RNAs by RBPs being part of a highly organized and versatile post-transcriptional regulatory system.