A zipcode unzipped

Abstract

RNA-binding proteins (RBPs) exert many roles in the post-transcriptional regulation of gene expression in eukaryotic cells. However, our understanding of how they recognize their target RNAs in vivo remains limited. In the January 1, 2012, issue of Genes & Development, Patel and colleagues (p. 43-53) provide detailed mechanistic insights into how one of the best-studied RBPs, zipcode-binding protein 1 (ZBP1), recognizes a bipartite RNA sequence element within the β-actin mRNA.

Figure 1.

Intra- and intermolecular cooperativity models of RBPs and their substrate recognition. Shown in the center are unstructured (left center panel) and structured (right center panel) RNAs. (Box 1) In the case of ZBP1, it recognizes an RNA zipcode in the β-actin transcript and binds the RNA via two KH domains forcing a conformational change in the RNA. (Box 2) For Egl and BicD, the RBP Egl recognizes the stem–loop of K10 RNA. Subsequent binding of the dynein adaptor BicD to Egl then increases its affinity for RNA. (Box 3) For She2p and She3p, both proteins cooperate together for ASH1 RNA binding. Proteins are depicted as colored spheres, and RNA is shown as black lines.