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

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 an...

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Main Author: Di Paolo, Andrés (author)
Other Authors: Eastman, Guillermo (author), Mesquita-Ribeiro, R. (author), Farías, Joaquina (author), Macklin, A. (author), Kislingerd, T. (author), Colburn, N. (author), Munroe, D. J. (author), Sotelo Sosa, José Roberto (author), Dajas-Bailador, F. (author), Sotelo-Silveira, José Roberto (author)
Format: article
Language:English
Published: 2020
Subjects:
Online Access:https://hdl.handle.net/20.500.12008/31761
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author Di Paolo, Andrés
author2 Eastman, Guillermo
Mesquita-Ribeiro, R.
Farías, Joaquina
Macklin, A.
Kislingerd, T.
Colburn, N.
Munroe, D. J.
Sotelo Sosa, José Roberto
Dajas-Bailador, F.
Sotelo-Silveira, José Roberto
author2_role author
author
author
author
author
author
author
author
author
author
author_browse Colburn, N.
Dajas-Bailador, F.
Di Paolo, Andrés
Eastman, Guillermo
Farías, Joaquina
Kislingerd, T.
Macklin, A.
Mesquita-Ribeiro, R.
Munroe, D. J.
Sotelo Sosa, José Roberto
Sotelo-Silveira, José Roberto
author_facet Di Paolo, Andrés
Eastman, Guillermo
Mesquita-Ribeiro, R.
Farías, Joaquina
Macklin, A.
Kislingerd, T.
Colburn, N.
Munroe, D. J.
Sotelo Sosa, José Roberto
Dajas-Bailador, F.
Sotelo-Silveira, José Roberto
author_role author
collection COLIBRI
dc.contributor.none.fl_str_mv Di Paolo Andrés, IIBCE
Eastman Guillermo, IIBCE
Mesquita-Ribeiro R.
Farías Joaquina, IIBCE
Macklin A.
Kislingerd T.
Colburn N.
Munroe D.
Sotelo Sosa José Roberto, IIBCE
Dajas-Bailador F.
Sotelo-Silveira José Roberto, IIBCE
dc.creator.none.fl_str_mv Di Paolo, Andrés
Eastman, Guillermo
Mesquita-Ribeiro, R.
Farías, Joaquina
Macklin, A.
Kislingerd, T.
Colburn, N.
Munroe, D. J.
Sotelo Sosa, José Roberto
Dajas-Bailador, F.
Sotelo-Silveira, José Roberto
dc.date.none.fl_str_mv 2020
2022-06-01T11:38:54Z
2022-06-01T11:38:54Z
dc.format.none.fl_str_mv 34 h.
application/pdf
dc.identifier.none.fl_str_mv Di Paolo, A, Eastman, G, Mesquita-Ribeiro, R, [y otros] "PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses". RNA. [en línea] 2020, 26:1637–1653. 34 h. DOI: 10.1261/rna.0755424.120
1469-9001
https://hdl.handle.net/20.500.12008/31761
10.1261/rna.075424.120
dc.language.none.fl_str_mv en
eng
dc.publisher.none.fl_str_mv RNA Society
dc.relation.none.fl_str_mv RNA, 2020, 26:1637–1653
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Licencia Creative Commons Atribución (CC - By 4.0)
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.none.fl_str_mv Programmed Cell Death 4 (PDCD4)
Axonal growth
Axonal regeneration
Ribosome profiling
Translation
dc.title.none.fl_str_mv PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
dc.type.none.fl_str_mv Artículo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
description 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.
eu_rights_str_mv openAccess
format article
id anni_66ae982e4665ee69dbcd44579973d281
identifier_str_mv Di Paolo, A, Eastman, G, Mesquita-Ribeiro, R, [y otros] "PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses". RNA. [en línea] 2020, 26:1637–1653. 34 h. DOI: 10.1261/rna.0755424.120
1469-9001
10.1261/rna.075424.120
instacron_str Universidad de la República
institution Universidad de la República
instname_str Universidad de la República
language eng
language_invalid_str_mv en
network_acronym_str anni
network_name_str oai-lr-anni
oai_identifier_str oai:colibri.udelar.edu.uy:20.500.12008/31761
publishDate 2020
publishDateSort 2020
publisher.none.fl_str_mv RNA Society
reponame_str COLIBRI
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responsesDi Paolo, AndrésEastman, GuillermoMesquita-Ribeiro, R.Farías, JoaquinaMacklin, A.Kislingerd, T.Colburn, N.Munroe, D. J.Sotelo Sosa, José RobertoDajas-Bailador, F.Sotelo-Silveira, José RobertoProgrammed Cell Death 4 (PDCD4)Axonal growthAxonal regenerationRibosome profilingTranslationProgrammed 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.RNA SocietyDi Paolo Andrés, IIBCEEastman Guillermo, IIBCEMesquita-Ribeiro R.Farías Joaquina, IIBCEMacklin A.Kislingerd T.Colburn N.Munroe D.Sotelo Sosa José Roberto, IIBCEDajas-Bailador F.Sotelo-Silveira José Roberto, IIBCE2022-06-01T11:38:54Z2022-06-01T11:38:54Z2020Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion34 h.application/pdfDi Paolo, A, Eastman, G, Mesquita-Ribeiro, R, [y otros] "PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses". RNA. [en línea] 2020, 26:1637–1653. 34 h. DOI: 10.1261/rna.0755424.1201469-9001https://hdl.handle.net/20.500.12008/3176110.1261/rna.075424.120reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengRNA, 2020, 26:1637–1653Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/317612026-04-14T10:09:47Z
spellingShingle PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
Di Paolo, Andrés
Programmed Cell Death 4 (PDCD4)
Axonal growth
Axonal regeneration
Ribosome profiling
Translation
status_str publishedVersion
title PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
title_full PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
title_fullStr PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
title_full_unstemmed PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
title_short PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
title_sort PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
topic Programmed Cell Death 4 (PDCD4)
Axonal growth
Axonal regeneration
Ribosome profiling
Translation
url https://hdl.handle.net/20.500.12008/31761