PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses

Di Paolo, Andres Pablo; Eastman, Guillermo; Mesquita Ribeiro, Raquel; Farias, Joaquina; Macklin, Andrew; Kislinger, Thomas; Colburn, Nancy; Munroe, David; Sotelo Sosa, Jose Roberto; Dajas Bailador, Federico; Sotelo Silveira, Jose Roberto

Abstract

© 2020 Di Paolo et al. Programmed cell death 4 (PDCD4) protein is a tumor 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. Using loss- and gain-of-function experiments in cortical and dorsal root ganglia primary neurons, we demonstrated 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.

Citation

Di Paolo, A. P., Eastman, G., Mesquita Ribeiro, R., Farias, J., Macklin, A., Kislinger, T., …Sotelo Silveira, J. R. (2020). PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses. RNA, 26(11), 1637-1653. https://doi.org/10.1261/rna.075424.120

• Journal Article Type: Article
• Acceptance Date: Jul 20, 2020
• Online Publication Date: Aug 3, 2020
• Publication Date: Nov 1, 2020
• Deposit Date: Sep 30, 2020
• Publicly Available Date: Oct 5, 2020
• Journal: RNA
• Print ISSN: 1355-8382
• Electronic ISSN: 1469-9001
• Publisher: Cold Spring Harbor Laboratory Press
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 11
• Pages: 1637-1653
• DOI: https://doi.org/10.1261/rna.075424.120
• Keywords: Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/4816546
• Publisher URL: https://rnajournal.cshlp.org/content/26/11/1637