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 transcript of 3.6 kb (15-LOX mRNA2) was detected containing a 1019 nt longer 3'-untranslated region (UTR2) than the main 2.6 kb mRNA (15-LOX mRNA1). In anaemic animals, northern blotting showed that 15-LOX mRNA2 was predominantly expressed in non-erythroid tissues, whereas 15-LOX mRNA1 was exclusively expressed 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 motif is related but not identical to the 10-fold repetitive differentiation control 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 translation. From tissues expressing the long 15-LOX mRNA2, two to three unidentified polypeptides with molecular weights of 53-55 and 90-93 kDa which bound to DICE2 were isolated by RNA affinity chromatography. A 93 kDa protein from lung cytosol, which was selected by DICE2 binding, was able to suppress 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 translational control of 15-LOX synthesis is discussed. Furthermore, the 3'-terminal part of the highly related rabbit leukocyte-type 12-LOX gene was analysed. Very similar repetitive CU-rich elements of the type DICE1 (20 repeats) and DICE2 (nine repeats) were found in the part corresponding to the 3'-UTR of the mRNA.
Thiele
B J
BJ
Institute of Biochemistry, University Clinics Charité, Humboldt-University Berlin, Hessische Strasse 3-4, D-10115 Berlin, Germany.
Berger
M
M
Huth
A
A
Reimann
I
I
Schwarz
K
K
Thiele
H
H
D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000378:metabolism; D011817:Rabbits
D020413:3' Untranslated Regions; D018076:DNA, Complementary; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase