TRANSLATION OF 15-LIPOXYGENASE MESSENGER-RNA IS INHIBITED BY A PROTEIN THAT BINDS TO A REPEATED SEQUENCE IN THE 3' UNTRANSLATED REGION

During red blood cell differentiation, the mRNA encoding rabbit erythr oid 15-lipoxygenase (LOX) is synthesized in the early stages of erythr opoiesis, but is only activated for translation in peripheral reticulo cytes. Erythroid LOX, which like other lipoxygenases catalyses the deg radation of lipids, is unique in its ability to attack intact phosphol ipids and is the main factor responsible for the degradation of mitoch ondria during reticulocyte maturation. Strikingly, rabbit erythroid LO X mRNA has 10 tandem repeats of a slightly varied, pyrimidine-rich 19 nt motif in its 3'-untranslated region (3'-UTR). In this study we demo nstrate, using gel retardation and UV-crosslinking assays, that this 3 '-UTR segment specifically binds a 48 kDa reticulocyte protein. Furthe rmore, the interaction between the 3'-UTR LOX repeat motif and the 48 kDa protein, purified to homogeneity by specific RNA chromatography, i s shown to be necessary and sufficient for specific translational repr ession of LOX as well as reporter mRNAs in vitro. To our knowledge thi s is the first case in which translation, presumably at the initiation step, is regulated by a defined protein-RNA interaction in the 3'-UTR .