ИСТИНА

It is known that regulation of translation of protein kinase MZeta (PKMZeta) in dendrites is critical for maintaining of long-term memory. Still it is little known about molecular mechanisms of this process. Earlier it was shown that 5"UTR of PKMZeta mRNA is required for its in vitro translation in WGE. Translational control under PKMZeta regulatory elements could be direct using UTRs or indirect using the mechanism of the total translational repression in dendrites. We have tested the role of regulatory elements of the PKMZeta mRNA in translational control in dendrites transfecting primary neuron culture by constructs containing different parts of leader sequence from PKMZeta. It is known that 5?UTR of PKMZeta contains six ORFs. We have shown that in vitro on the ORF-6 48S ribosomal initiation complex is formed. Then we mutated start ATG codon of ORF-6 to TAG stop codon and tested such construction in the primary neuron culture. Substitution of only two nucleotides in the 500 nt leader sequence strongly activated translation in dendrites. So translational repression of mRNA with PKMZeta UTRs in dendrites depends on ribosomal initiation complex on the ORF-6. We suppose that translational silencing of PKMZeta gene is realized by upstream ORFs in 5?UTR.