Project description
Understanding how neurons grow
Neurons are unique cells because their axons can grow incredibly long, far longer than the size of their cell bodies. While we know that neurons elongate during early development and as the organism matures, the processes behind this growth are not well understood. It is necessary to identify the molecular mechanisms that guide this process. With this in mind, the ERC-funded GrowthSINE project will study a special type of RNA called growth-inducing SINEs (GI-SINEs). These RNAs play a key role in axon growth, interacting with proteins that help neurons grow. By exploring how GI-SINEs regulate growth, the project hopes to uncover new insights into how neurons develop and how growth is controlled at a molecular level.
Objective
Neurons are the longest cells, extending axons over distances that can reach four orders of magnitude larger than their cell body diameters. How can they achieve such long distance growth? After initial engagement with target cells, neurons undergo stretch-induced elongation as the nervous system matures with the growth of the organism. The molecular mechanisms enabling such prodigious growth are unknown. Based on strong preliminary evidence, we tested the hypothesis that both the initial elongating and later stretch-induced axon growth act via a shared RNA localization mechanism.
Very strikingly, we identified a specific subset of polyadenylated repeat element RNAs, hereby termed growth-inducing SINEs (GI-SINEs), as key growth regulators. GI-SINEs are induced from AP-1 promoter-associated extragenic loci, and interact with ribosomal proteins and the axon growth regulating RNA binding protein nucleolin, in neuronal cytoplasm. We will elucidate how this intrinsic mechanism controls neuron growth, determining (1) how known elongating growth regulators affect stretch-induced growth; (2) how local and global protein synthesis regulate neuron growth control; and (3) how growth regulates the GI-SINEs and how they regulate different growth modalities.
We will apply a multidisciplinary suite of techniques and approaches to these challenges, including a new technology for characterization of nascent proteomes developed in-house. The proposed project will provide ground-breaking and fundamental mechanistic insights on neuronal growth, and will establish novel methods that will be widely applicable. Moreover, establishing that a repeat element RNA is an intrinsic effector linking AP-1 transcription to translation regulation is a breakthrough finding that opens new horizons for cell biology and neuroscience.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsRNA
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Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
7610001 Rehovot
Israel