The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency

Abstract

The cap structure and the poly(A) tail are important regulatory determinants in establishing the translational efficiency of a messenger RNA. Although the mechanism by which either determinant functions remains poorly characterized, the interaction between the poly(A) tail-poly(A)-binding protein complex and events occurring at the 5' terminus during translation initiation has been an intriguing possibility. In this report, the mutual dependence of the cap and the poly(A) tail was studied. Poly(A)+ and poly(A)- luciferase (Luc) mRNAs generated in vitro containing or lacking a cap were translated in vivo in tobacco protoplasts, Chinese hamster ovary cells, and yeast following delivery by electroporation. The poly(A) tail-mediated regulation of translational efficiency was wholly dependent on the cap for function. Moreover, cap function was enhanced over an order of magnitude by the presence of a poly(A) tail. The relative differences in stability between the mRNAs could not account for the synergism. The synergism between the cap and poly(A) tail was not observed in yeast cells in which active translation had been disrupted. In addition, the synergism was not observed in in vitro translation lysates. These data demonstrate that the cap and the poly(A) tail are interdependent for optimal function in vivo and suggest that communication between the two regulatory determinants may be important in establishing efficient translation.