Speaker
Description
Neurons mediate the reception and transmission of nervous stimuli with their polarized shape and processes. Each nervous cell makes thousands of synaptic contacts with other cells. Synapses are well characterized in their protein content but there is less concordance about the resident RNA species that contribute to synapse function and maintenance. mRNAs that localize at synaptic boutons can undergo local translation and produce synaptic proteins, and also non-coding RNA species like lncRNAs, miRNAs and circRNAs could play a fundamental but still uncharacterized role in synapse biology. Furthermore, many studies focused on mouse models, while the human synaptic transcriptome remains still unexplored. Recent evidence shows that synaptic aberrations might represent a shared pathological feature across some neurodegenerative diseases like Amyotrophic Lateral Sclerosis, an illness specifically targeting motoneurons. In this study we characterize the human synaptic transcriptome of in vitro iPSC-derived motoneurons. We exploit an adaptation of the mouse brain synaptosome isolation protocol, to isolate the motoneuron synaptosome-associated RNAs. With these techniques, we aim at identifying the molecular mechanisms that underlie the synaptic localization of coding and non-coding RNAs and their local function. We aim to analyze the differences between wild type ad ALS motoneuron synapses with mutations in the FUS protein, that are associated with a juvenile and aggressive form of ALS. In mice, FUS also localizes at the pre-synaptic compartment and a recent report outlined that its synaptic accumulation upon NLS deletion triggers early misregulation of synaptic RNAs (Sahadevan et al., 2021). With this work we aim at the characterization of the human synaptome to highlight the RNA contribution to synapse function and ultimately degeneration.
| Author(s) | Vittorio Padovano*1,2, Adriano Setti1, Flaminia Pellegrini1, Tiziana Santini1, Fabio Gennaro Fiorella1, Davide Mariani3, Nicolò Glaudo1, Julie Martone4, Irene Bozzoni1,2,3 |
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| Affiliation(s) | "1 Department of Biology and Biotechnologies “Charles Darwin”, Sapienza University of Rome; 00185, Rome, Italy. 2 Center for Life Nano- & Neuro-Science@Sapienza of Istituto Italiano di Tecnologia (IIT); Rome, 00161, Italy. 3 Center for Human Technologies (CHT) Istituto Italiano di Tecnologia (IIT); 16152 Genova, Italy. 4Institute of Molecular Biology and Pathology, CNR; Rome, 00185, Italy." |
