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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| Other Authors: | , , , , , , , , , |
| Format: | article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/20.500.12008/31761 |
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| _version_ | 1868890081753825280 |
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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 |