%0 Journal Article
%T Insights from a Paradigm Shift: How the Poly(A)-Binding Protein Brings Translating mRNAs Full Circle
%A Daniel R. Gallie
%J New Journal of Science
%D 2014
%R 10.1155/2014/873084
%X In recent years, our thinking of how the initiation of protein synthesis occurs has changed dramatically. Initiation was thought to involve only events occurring at or near the 5กไ-cap structure, which serves as the binding site for the cap-binding complex, a group of translation initiation factors (eIFs) that facilitate the binding of the 40 S ribosomal subunit to an mRNA. Because the poly(A)-binding protein (PABP) binds the poly(A) tail present at the 3กไ-terminus of an mRNA, it was long thought to play no role in translation initiation. In this review, I present evidence from my laboratory that has contributed to the paradigm shift in how we think of mRNAs during translation. The depiction of mRNAs as straight molecules in which the poly(A) tail is far from events occurring at the 5กไ-end has now been replaced by the concept of a circular mRNA where the interaction between PABP and the cap-binding complex bridges the termini of an mRNA and promotes translation initiation. The research from my laboratory supports the new paradigm that translation of most mRNAs requires a functional and physical interaction between the termini of an mRNA. 1. Introduction Our understanding of how mRNAs are translated into proteins has undergone a paradigm shift in recent years. Prior to this shift, a translating mRNA undergoing translation was thought of as a straight molecule and protein synthesis was considered a linear process that encompassed three phases. In this prior view, the first phase, that is, translation initiation, begins with events that only involve the 5กไ-end of an mRNA in which the subunits of a ribosome are recruited and assembled at the initiation codon and conclude with the synthesis of the first peptide bond (Figure 1). This is followed by the elongation phase, that is, the ribosome-catalyzed decoding of the open reading frame into protein and finally the recognition of the stop codon and release of the nascent peptide from the ribosome. In this paper, I will illustrate how our understanding of how mRNAs undergoing translation in eukaryotes fundamentally changed from a view in which translation initiation is orchestrated by events only involving the 5กไ-end of an mRNA to one in which the mRNA is circularized by functional and physical interactions between the termini of an mRNA. As my research involves translation in plants, findings from this kingdom this will be emphasized. However, the similarities and differences in the interactions of the machinery involved in ribosome recruitment in plants and those of other eukaryotes will be also be discussed.
%U http://www.hindawi.com/journals/njos/2014/873084/