The histone 3'-terminal stem-loop is necessary for translation in Chinese hamster ovary cells

The metazoan cell cycle-regulated histone mRNAs are the only known cellular mRNAs that do not terminate in a poly(A) tail. Instead, mammalian histone mRNAs terminate in a highly conserved stem-loop structure which is required for 3'-end processing and regulates mRNA stability. The poly(A) tail not only regulates translational efficiency and mRNA stability but is required for the function of the cap in translation (m(7)GpppN), We show that the histone terminal stem-loop is functionally similar to a poly(A) tail in that it enhances translational efficiency and is co-dependent on a cap in order to establish an efficient level of translation. The histone stem-loop is sufficient and necessary to increase the translation of reporter mRNA in transfected Chinese hamster ovary cells but must be positioned at the 3'-terminus in order to function optimally. Mutations within the conserved stem or loop regions reduced its ability to facilitate translation. All histone mRNAs in higher plants are polyadenylated. The histone stem-loop did not function to influence translational efficiency or mRNA stability in plant protoplasts. These data demonstrate that the histone stem-loop directs efficient translation and that it is functionally analogous to a poly(A) tail.