Long-Term Memory Formation in <i>Drosophila</i> Depends on the 3′UTR of CPEB Gene <i>orb2</i>
Eugene N. Kozlov,
Elena V. Tokmatcheva,
Anastasia M. Khrustaleva,
Eugene S. Grebenshchikov,
Roman V. Deev,
Rudolf A. Gilmutdinov,
Lyubov A. Lebedeva,
Mariya Zhukova,
Elena V. Savvateeva-Popova,
Paul Schedl,
Yulii V. Shidlovskii
Affiliations
Eugene N. Kozlov
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Elena V. Tokmatcheva
Institute of Physiology, Russian Academy of Sciences, 188680 St. Petersburg, Russia
Anastasia M. Khrustaleva
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Eugene S. Grebenshchikov
Department of Biology and General Genetics, Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, Russia
Roman V. Deev
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Rudolf A. Gilmutdinov
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Lyubov A. Lebedeva
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Mariya Zhukova
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Elena V. Savvateeva-Popova
Institute of Physiology, Russian Academy of Sciences, 188680 St. Petersburg, Russia
Paul Schedl
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Yulii V. Shidlovskii
Laboratory of Gene Expression Regulation in Development, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia
Activation of local translation in neurites in response to stimulation is an important step in the formation of long-term memory (LTM). CPEB proteins are a family of translation factors involved in LTM formation. The Drosophila CPEB protein Orb2 plays an important role in the development and function of the nervous system. Mutations of the coding region of the orb2 gene have previously been shown to impair LTM formation. We found that a deletion of the 3’UTR of the orb2 gene similarly results in loss of LTM in Drosophila. As a result of the deletion, the content of the Orb2 protein remained the same in the neuron soma, but significantly decreased in synapses. Using RNA immunoprecipitation followed by high-throughput sequencing, we detected more than 6000 potential Orb2 mRNA targets expressed in the Drosophila brain. Importantly, deletion of the 3′UTR of orb2 mRNA also affected the localization of the Csp, Pyd, and Eya proteins, which are encoded by putative mRNA targets of Orb2. Therefore, the 3′UTR of the orb2 mRNA is important for the proper localization of Orb2 and other proteins in synapses of neurons and the brain as a whole, providing a molecular basis for LTM formation.