Growing Long Distance – RNA Control of Neuronal Extension

Title	Growing Long Distance – RNA Control of Neuronal Extension
Acronym	GrowthSINE
Start date	2024-10-01
End date	2029-09-30
Sponsor	European Research Council - Advanced Grant (ERC-AdG)
Institution	Weizmann Institute of Science

Associated cell lines

• UCSFi001-A (GM25256, WTC, WTC11, wtc11, Wtc11)
• WAe009-A (H9, WA09)

Project Description

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.