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

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

Resumen:

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.


Detalles Bibliográficos
2020
Programmed Cell Death 4 (PDCD4)
Axonal growth
Axonal regeneration
Ribosome profiling
Translation
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/31761
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)
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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_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
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collection COLIBRI
dc.contributor.filiacion.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.accessioned.none.fl_str_mv 2022-06-01T11:38:54Z
dc.date.available.none.fl_str_mv 2022-06-01T11:38:54Z
dc.date.issued.none.fl_str_mv 2020
dc.description.abstract.none.fl_txt_mv 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.
dc.format.extent.es.fl_str_mv 34 h.
dc.format.mimetype.es.fl_str_mv application/pdf
dc.identifier.citation.es.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
dc.identifier.doi.none.fl_str_mv 10.1261/rna.075424.120
dc.identifier.issn.none.fl_str_mv 1469-9001
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/31761
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv RNA Society
dc.relation.ispartof.es.fl_str_mv RNA, 2020, 26:1637–1653
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.es.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.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv 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
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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
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institution Universidad de la República
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publishDate 2020
reponame_str COLIBRI
repository.mail.fl_str_mv mabel.seroubian@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
repository_id_str 4771
rights_invalid_str_mv Licencia Creative Commons Atribución (CC - By 4.0)
spelling Di 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, IIBCE2022-06-01T11:38:54Z2022-06-01T11:38:54Z2020Di 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.075424.120Programmed 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.Submitted by Verdun Juan Pablo (jverdun@fcien.edu.uy) on 2022-05-30T22:48:47Z No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.1261rna.075424.120.pdf: 3928275 bytes, checksum: 04c612b4331181230e083e508676ddc6 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2022-06-01T11:29:45Z (GMT) No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.1261rna.075424.120.pdf: 3928275 bytes, checksum: 04c612b4331181230e083e508676ddc6 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2022-06-01T11:38:54Z (GMT). No. of bitstreams: 2 license_rdf: 19875 bytes, checksum: 9fdbed07f52437945402c4e70fa4773e (MD5) 10.1261rna.075424.120.pdf: 3928275 bytes, checksum: 04c612b4331181230e083e508676ddc6 (MD5) Previous issue date: 202034 h.application/pdfenengRNA SocietyRNA, 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)Programmed Cell Death 4 (PDCD4)Axonal growthAxonal regenerationRibosome profilingTranslationPDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responsesArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaDi Paolo, AndrésEastman, GuillermoMesquita-Ribeiro, R.Farías, JoaquinaMacklin, A.Kislingerd, T.Colburn, N.Munroe, D. J.Sotelo Sosa, José RobertoDajas-Bailador, F.Sotelo Silveira, José RobertoORIGINAL10.1261rna.075424.120.pdf10.1261rna.075424.120.pdfapplication/pdf12961402http://localhost:8080/xmlui/bitstream/20.500.12008/31761/6/10.1261rna.075424.120.pdf1a676320e4641631ed9a017f8d6af6cdMD56LICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/31761/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; charset=utf-844http://localhost:8080/xmlui/bitstream/20.500.12008/31761/2/license_urla0ebbeafb9d2ec7cbb19d7137ebc392cMD52license_textlicense_texttext/html; charset=utf-838395http://localhost:8080/xmlui/bitstream/20.500.12008/31761/3/license_textd606c60c5d78967c4ed7a729e5bb402fMD53license_rdflicense_rdfapplication/rdf+xml; charset=utf-819875http://localhost:8080/xmlui/bitstream/20.500.12008/31761/4/license_rdf9fdbed07f52437945402c4e70fa4773eMD5420.500.12008/317612022-06-07 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- Universidad de la Repúblicafalse
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