The polyadenlyate binding protein (PABP) and translational control /

Translation is the process by which proteins are synthesized from messenger RNAs. This complex process is regulated by a multitude of factors (1). One such factor is the Polyadenylate Binding Protein (PABP), an abundant protein associated with messenger ribonucleoprotein particles (mRNPs) (18). As a result of its interaction with both poly(A) RNA and eukaryotic initiation factor 4G (eIF4G), a component of the tripartite eIF4F cap-binding complex, PABP elicits mRNA circularization and stimulates translation (2). Although the mechanism by which mRNA circularization facilitates translation is not clear, one model suggests that circularization promotes ribosome recycling. Recently, an interaction between PABP and the termination factor, eukaryotic Release Factor3 (eRF3/GSPT) was demonstrated in mammals (71). By interacting with both eRF3 and eIF4G, it was postulated that PABP physically bridges the stop codon to the 5' cap structure, enabling terminating ribosomes to reinitiate translation on the same mRNA. To explore this idea, several PABP mutants lacking the ability to bind eRF3 were generated and added to a PABP-depleted Krebs-2 Cell-Free Extract to study the effects on translation. The PABP mutants stimulated translation as effectively as wild-type PABP, suggesting that the eRF3-PABP interaction is dispensable for translation and ribosome recycling. RNA-binding protein localization may be regulated by methylation and protein-protein interactions (98). PABP was also recently identified as a Coactivator-Associated Arginine Methyltransferase I (CARMI) substrate (23). Here, we show that PABP methylation does not modulate nuclear shuttling or its interactions with 14-3-3, a novel PABP-interacting protein. Translation in "non-nuclear" rabbit reticulocyte lysate is robust and PABP-independent, suggesting a loss of inhibitory control by nuclear factors. We reveal for the first time that the general RNA-binding protein YB-1 renders translation i