PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
- Andres Pablo Di Paolo1,
- Guillermo Eastman1,
- Raquel Mesquita Ribeiro2,
- Joaquina Farias1,
- Andrew Macklin3,
- Thomas Kislinger4,
- Nancy Colburn5,
- David Munroe6,
- Jose Roberto Sotelo Sosa1,
- Federico Dajas Bailador2 and
- Jose Roberto Sotelo Silveira7,8
- 1 Instituto de Investigaciones Biologicas Clemente Estable;
- 2 School of Life Sciences, University of Nottingham;
- 3 Princess Margaret Cancer Centre, University Health Network, Toronto;
- 4 Princess Margaret Cancer Centre, University Health Network and University of Toronto;
- 5 National Cancer Institute (NIH), Frederick, MD, USA (Deceased);
- 6 LEIDOS at Frederick National Laboratory for Cancer Research, Frederick, MD, USA (Deceased);
- 7 Instituto de Investigaciones Biologicas Clemente Estable, Facultad de Ciencias
- ↵* Corresponding author; email: sotelojos{at}gmail.com
Abstract
Programmed Cell Death 4 (PDCD4) protein is a tumour suppressor that inhibits translation through the mTOR dependent initiation factor EIF4A, but its functional role and mRNA targets in neurons remain largely unknown. Our work identified that PDCD4 is highly expressed in axons and dendrites of CNS and PNS neurons, with loss and gain of function experiments in cortical and dorsal root ganglia primary neurons demonstrating the capacity of PDCD4 to negatively control axonal growth. To explore PDCD4 transcriptome and translatome targets we used Ribo-Seq and uncovered a list of potential targets with known functions as axon/neurite outgrowth regulators. In addition, we observed that PDCD4 can be locally synthesized in adult axons in vivo and its levels decrease at the site of peripheral nerve injury and before nerve regeneration. Overall, our findings demonstrate that PDCD4 can act as a new regulator of axonal growth via the selective control of translation, providing a target mechanism for axon regeneration and neuronal plasticity processes in neurons.
Keywords
- Received March 22, 2020.
- Accepted July 20, 2020.
- Published by Cold Spring Harbor Laboratory Press for the RNA Society
This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
