The role of CPEB family proteins in the nervous system function in the norm and pathology

Eugene Kozlov,Yulii V Shidlovskii,Rudolf Gilmutdinov,Mariya Zhukova,Paul Schedl

doi:10.1186/s13578-021-00577-6

Abstract

Posttranscriptional gene regulation includes mRNA transport, localization, translation, and regulation of mRNA stability. CPEB (cytoplasmic polyadenylation element binding) family proteins bind to specific sites within the 3′-untranslated region and mediate poly- and deadenylation of transcripts, activating or repressing protein synthesis. As part of ribonucleoprotein complexes, the CPEB proteins participate in mRNA transport and localization to different sub-cellular compartments. The CPEB proteins are evolutionarily conserved and have similar functions in vertebrates and invertebrates. In the nervous system, the CPEB proteins are involved in cell division, neural development, learning, and memory. Here we consider the functional features of these proteins in the nervous system of phylogenetically distant organisms: Drosophila, a well-studied model, and mammals. Disruption of the CPEB proteins functioning is associated with various pathologies, such as autism spectrum disorder and brain cancer. At the same time, CPEB gene regulation can provide for a recovery of the brain function in patients with fragile X syndrome and Huntington's disease, making the CPEB genes promising targets for gene therapy.

Highlights

The functioning of the nervous system is based on the ability of neurons to perceive, transmit, and store information encoded in electrical and chemical signals
Since amyloids are stable and capable of self-maintenance, synapse-specific and self-sustaining activation of mRNA translation of Cytoplasmic polyadenylation element binding (CPEB) protein target genes ensures the accumulation of proteins near the synapse, which is necessary for longterm potentiation associated with learning and long-term memory
The functioning of the CPEB family proteins is essential at all stages of ontogeny

Summary

Introduction

The functioning of the nervous system is based on the ability of neurons to perceive, transmit, and store information encoded in electrical and chemical signals. Repetitive stimuli lead to changes in the neuron nucleus, such as induction of the transcriptional activator CREB1 (cAMP response element binding protein 1) and inactivation of the transcriptional repressor CREB2 [34], triggering the synthesis of mRNAs necessary for long-term facilitation (for more detail on the participants in the process, see [34]).

Results

Conclusion