Tissue-specific translational regulation of alternative rabbit 15-lipoxygenase mRNAs differing in their 3 '-untranslated regions

By screening a rabbit reticulocyte library, an alternative 15-LOX transcrip t of 3.6 kb (15-LOX mRNA2) was detected containing a 1019 nt longer 3'-untr anslated region (UTR2) than the main 2.6 kb mRNA (15-LOX mRNA1), In anaemic animals, northern blotting showed that 15-LOX mRNA2 was predominantly expr essed in non-erythroid tissues, whereas 15-LOX mRNA1 was exclusively expres sed in red blood cells and bone marrow. The 15-LOX 3'-UTR2 mRNA2 contained a novel 8-fold repetitive CU-rich motif, 23 nt in length (DICE2), This moti f is related but not identical to the 10-fold repetitive differentiation co ntrol element (DICE1) of 19 nt residing in the 15-LOX UTR1 mRNA1, DICE1 was shown to interact with human hnRNP proteins E1 and K, thereby inhibiting t ranslation, From tissues expressing the long 15-LOX mRNA2, two to three uni dentified polypeptides with molecular weights of 53-55 and 90-93 kDa which bound to DICE2 were isolated by RNA affinity chromatography. A 93 kDa prote in from lung cytosol, which was selected by DICE2 binding, was able to supp ress translational inhibition of 15-LOX mRNA2, but not of 15-LOX mRNA1, by hnRNP E1. A possible interaction between DICE1/DICE2 cis/trans factors in t ranslational control of 15-LOX synthesis is discussed. Furthermore, the 3'- terminal part of the highly related rabbit leukocyte-type 12-LOX gene was a nalysed. Very similar repetitive CU-rich elements of the type DICE1 (20 rep eats) and DICE2 (nine repeats) were found in the part corresponding to the 3'-UTR of the mRNA.