Deciphering the role of RNA-binding proteins in the post-transcriptional control of gene expression

Abstract

Eukaryotic cells express a large variety of ribonucleic acid-(RNA)-binding proteins (RBPs) with diverse affinity and specificity towards target RNAs that play a crucial role in almost every aspect of RNA metabolism. In addition, specific domains in RBPs impart catalytic activity or mediate protein-protein interactions, making RBPs versatile regulators of gene expression. In this review, we elaborate on recent experimental and computational approaches that have increased our understanding of RNA-protein interactions and their role in cellular function. We review aspects of gene expression that are modulated post-transcriptionally by RBPs, namely the stability of polymerase II-derived mRNA transcripts and their rate of translation into proteins. We further highlight the extensive regulatory networks of RBPs that implement a combinatorial control of gene expression. Taking cues from the recent development in the field, we argue that understanding spatio-temporal RNA-protein association on a transcriptome level will provide invaluable and unexpected insights into the regulatory codes that define growth, differentiation and disease.

Figure 1:

Footprints of several RBPs (CDS: coding sequence) on the p27 (Kip1) transcript are shown. Information on RBP-binding sites were obtained from 4-thiouridine CLIP performed on individual RBPs (see reference [96] and unpublished data from M.Z. lab). Overlapping RBP clusters suggest cross-talks between various RBPs that ultimately determine the fate of the p27 transcript.