An antisense-long-noncoding-RNA modulates p75NTR expression levels during neuronal polarization
Veronica De Paolis,
Nicoletta Paolillo,
Tiziano Siri,
Alessandra Grosso,
Veronica Lorello,
Cristina Spina,
Gabriele Caporali,
Federico La Regina,
Beatrice Vignoli,
Corinna Giorgi
Affiliations
Veronica De Paolis
Department of Experimental Medicine, University of Rome ''Tor Vergata'', Via Montpellier 1, 00133 Rome, Italy; European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Institute of Biochemistry and Cell Biology, National Research Council of Italy (IBBC-CNR), Via Ercole Ramarini 32, 00015 Monterotondo, Italy
Nicoletta Paolillo
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy
Tiziano Siri
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Department of Sciences, University of Roma Tre, Viale Guglielmo Marconi 446, 00146 Rome, Italy; CERVO Brain Research Center, Quebec City, QC G1J 2G3, Canada
Alessandra Grosso
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Department of Biology and Biotechnology “Charles Darwin”, University of Rome “Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy
Veronica Lorello
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Department of Biology and Biotechnology “Charles Darwin”, University of Rome “Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy
Cristina Spina
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Department of Biology and Biotechnology “Charles Darwin”, University of Rome “Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy
Gabriele Caporali
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Department of Biology and Biotechnology “Charles Darwin”, University of Rome “Sapienza”, P.le Aldo Moro 5, 00185 Rome, Italy
Federico La Regina
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy
Beatrice Vignoli
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Department of Cellular, Computational and Integrative Biology – CIBIO, University of Trento, Via Sommarive 9, 38123 Povo TN, Italy; Corresponding author
Corinna Giorgi
European Brain Research Institute (EBRI), Fondazione Rita Levi-Montalcini, Viale Regina Elena 295, 00161 Rome, Italy; Institute of Molecular Biology and Pathology, National Research Council of Italy (IBPM-CNR), P.le Aldo Moro 5, 00185 Rome, Italy; Corresponding author
Summary: Proper polarization of newly generated neurons is a critical process for neural network formation and brain development. The pan-neurotrophin p75NTR receptor plays a key role in this process localizing asymmetrically in one of the differentiating neurites and specifying its axonal identity in response to neurotrophins. During axonal specification, p75NTR levels are transiently modulated, yet the molecular mechanisms underlying this process are not known. Here, we identified a previously uncharacterized natural antisense transcript, AS-p75, encoded within the p75NGFR mouse gene. Using an in vitro model of polarizing murine neurons, we found that AS-p75 and p75NTR display divergent expression profiles and that p75NTR expression levels increase upon competition or depletion of AS-p75, indicating that AS-p75 is a negative regulator of p75NTR expression. Depletion of AS-p75 also results in altered p75NTR subcellular distribution and affects the polarization process. Overall, our data uncovered AS-p75 as a modulator of p75NTR expression, offering new insights into the regulation of this neurotrophin receptor during in vitro neuronal polarization.
