PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses
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.
2020 | |
Programmed Cell Death 4 (PDCD4) Axonal growth Axonal regeneration Ribosome profiling Translation |
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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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bitstream.checksumAlgorithm.fl_str_mv | MD5 MD5 MD5 MD5 MD5 |
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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 |
format | article |
id | COLIBRI_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 | COLIBRI |
network_name_str | COLIBRI |
oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/31761 |
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 |