A tale of two termini: a functional interaction between the termini of an mRNA is a prerequisite for efficient translation initiation

Abstract

A quarter of century following the prediction that mRNAs are translated in a circular form, recent biochemical and genetic evidence has accumulated to support the idea that communication between the termini of an mRNA is necessary to promote translation initiation. The poly(A)-binding protein (PABP) interacts with the cap-associated eukaryotic initiation factor (eIF) 4G (in yeast and plants) and eIF4B (in plants), a functional consequence of which is to increase the affinity of PABP for poly(A) and to increase the affinity of the cap-binding complex, eIF4F (of which eIF4G is a subunit) for the 5' cap structure. In mammals, PABP interacts with a novel PABP-interacting protein that also binds eIF4A. The interaction between PABP and those initiation factors associated with the 5' terminus of an mRNA may also explain the role of PABP during mRNA turnover, as it protects the 5' cap from attack by Dcp1p, the decapping enzyme. Several of those mRNAs that have evolved functional equivalents to a cap or a poly(A) tail nevertheless require a functional interaction between terminal regulatory elements similar to that observed between the 5' cap and poly(A) tail, suggesting that efficient translation is predicated on communication between largely-separated regulatory elements within an mRNA.