RNA-binding proteins and post-transcriptional gene regulation

Abstract

RNAs in cells are associated with RNA-binding proteins (RBPs) to form ribonucleoprotein (RNP) complexes. The RBPs influence the structure and interactions of the RNAs and play critical roles in their biogenesis, stability, function, transport and cellular localization. Eukaryotic cells encode a large number of RBPs (thousands in vertebrates), each of which has unique RNA-binding activity and protein-protein interaction characteristics. The remarkable diversity of RBPs, which appears to have increased during evolution in parallel to the increase in the number of introns, allows eukaryotic cells to utilize them in an enormous array of combinations giving rise to a unique RNP for each RNA. In this short review, we focus on the RBPs that interact with pre-mRNAs and mRNAs and discuss their roles in the regulation of post-transcriptional gene expression.

Figure 1

RNA-binding proteins (RBPs) function in multiple cellular processes. Genetic information stored in chromosomal DNA is translated into proteins through mRNAs. This allows for post-transcriptional control of gene expression conferring a crucial role to the mRNA-binding proteins in this regulation. In addition to the RBPs associated with mRNA, many different classes of RBPs interact with various small non-coding RNAs to form ribonucleoprotein (RNP) complexes that are actively involved in many different aspects of cell metabolism, such as DNA replication, expression of histone genes, regulation of transcription and translational control.

Figure 2

RNA-binding domains of RBPs. Often, several RNA-binding domains are found within one RBP. Different RNA-binding domains include the RNA-binding domain (RBD), K-homology (KH) domain, RGG (Arg-Gly-Gly) box, double stranded RNA-binding domain (dsRBD), Piwi/Argonaute/Zwille (PAZ) domain, RNA helicase DEAD/DEAH box, RNA-binding zinc finger (ZnF) and Puf RNA-binding repeats (PUF). All are presented as colored boxes.

Figure 3

The function of RBPs in the regulation of post-transcriptional gene expression. Once pre-mRNAs are transcribed by RNA polymerase II in the nucleus, they undergo many different processing steps that can determine the fate of the transcript. During splicing, molecular imprinting of the exon-junction complex (EJC) occurs specifically on spliced mRNAs, and this event affects the fate of the mRNPs in the following steps, such as recruitment of ribosomal subunits for translation initiation, or surveillance of mRNA for nonsense-mediated mRNA decay (NMD). RBPs bound, for example, to the 3′UTR of an mRNA can repress the initiation of translation and direct the subcellular localization of the mRNAs. Some mRNAs, upon transport to the cytoplasm, are further modified by the cytoplasmic polyadenylation RNP, CPEB.