Poly(A) binding proteins: are they all created equal?

Poly(A) Binding Proteins (PABPs), represent a major class of regulatory proteins that interact with the 3’ poly(A) tail of mRNA. These highly conserved polypeptides are present only in eukaryotes; vertebrates express four PABPs in the cytoplasm and Arabidopsis expresses eight, in addition one nuclear PABP is expressed1. These cytoplasmic PABPs contain a conserved domain organization using RNA-recognition motifs, globular domains that are also present in other RNA binding proteins. Nuclear PABPs are structurally and functionally distinct from cytoplasmic PABPs and are involved in stimulating maturation of mRNA and export. Originally it was thought that PABPs’ role was to protect the mRNA from degradation by interacting with the poly (A) tail. However, a great number of studies have shown that PABPs can interact with other regulatory sequences in the RNA and protein factors, making the PABP family a key player in numerous pathways for gene expression. In protein synthesis, PABP binds the 3’ untranslated region (UTR) of mRNAs and has multiple functions in initiation of translation as well as binding to the 5’ UTR of PABP mRNA to possibly regulate its own expression2–4. PABP also functions in polyadenlyation, export, surveillance of transcripts, microRNA (miRNA) activity, control of mRNA stability and viral infection1, 5, 6. PABPs appear to lack catalytic activity of their own, but mediate the interactions of factors and RNAs that affect these processes. New roles are being discovered for this multi-functional class of proteins. However, little is known about the differences among the various PABPs. This review will highlight information, where available, on the differing functions of PABPs and new information on their roles in gene expression.