The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures
Resumen:
Cellular stress conditions activate p53-dependent pathways to counteract the inflicted damage. To achieve the required functional diversity, p53 is subjected to numerous post-translational modifications and the expression of isoforms. Little is yet known how p53 has evolved to respond to different stress pathways. The p53 isoform p53/47 (p47 or ΔNp53) is linked to aging and neural degeneration and is expressed in human cells via an alternative cap-independent translation initiation from the 2nd in-frame AUG at codon 40 (+118) during endoplasmic reticulum (ER) stress. Despite an AUG codon in the same location, the mouse p53 mRNA does not express the corresponding isoform in either human or mouse-derived cells. High-throughput in-cell RNA structure probing shows that p47 expression is attributed to PERK kinase-dependent structural alterations in the human p53 mRNA, independently of eIF2α. These structural changes do not take place in murine p53 mRNA. Surprisingly, PERK response elements required for the p47 expression are located downstream of the 2nd AUG. The data show that the human p53 mRNA has evolved to respond to PERKmediated regulation of mRNA structures in order to control p47 expression. The findings highlight how p53 mRNA co-evolved with the function of the encoded protein to specify p53-activities under different cellular conditions.
| 2023 | |
| Inglés | |
| Universidad de la República | |
| COLIBRI | |
| https://hdl.handle.net/20.500.12008/43176 | |
| Acceso abierto | |
| Licencia Creative Commons Atribución (CC - By 4.0) |
| _version_ | 1807522807816388608 |
|---|---|
| author | Fusée, L. T. S. |
| author2 | Salomao, Norman Ponnuswamy, Anand Wang, L. López Ferreira, Luis Ignacio Chen, Sa Gu, Xiaolian Polyzoidis, Stavros Gnanasundram, S Fahraeus, Robin |
| author2_role | author author author author author author author author author |
| author_facet | Fusée, L. T. S. Salomao, Norman Ponnuswamy, Anand Wang, L. López Ferreira, Luis Ignacio Chen, Sa Gu, Xiaolian Polyzoidis, Stavros Gnanasundram, S Fahraeus, Robin |
| author_role | author |
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| collection | COLIBRI |
| dc.contributor.filiacion.none.fl_str_mv | Fusée L. T. S. Salomao Norman Ponnuswamy Anand Wang L. López Ferreira Luis Ignacio, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología. Chen Sa Gu Xiaolian Polyzoidis Stavros Gnanasundram S Fahraeus Robin |
| dc.creator.none.fl_str_mv | Fusée, L. T. S. Salomao, Norman Ponnuswamy, Anand Wang, L. López Ferreira, Luis Ignacio Chen, Sa Gu, Xiaolian Polyzoidis, Stavros Gnanasundram, S Fahraeus, Robin |
| dc.date.accessioned.none.fl_str_mv | 2024-03-19T12:16:26Z |
| dc.date.available.none.fl_str_mv | 2024-03-19T12:16:26Z |
| dc.date.issued.none.fl_str_mv | 2023 |
| dc.description.abstract.none.fl_txt_mv | Cellular stress conditions activate p53-dependent pathways to counteract the inflicted damage. To achieve the required functional diversity, p53 is subjected to numerous post-translational modifications and the expression of isoforms. Little is yet known how p53 has evolved to respond to different stress pathways. The p53 isoform p53/47 (p47 or ΔNp53) is linked to aging and neural degeneration and is expressed in human cells via an alternative cap-independent translation initiation from the 2nd in-frame AUG at codon 40 (+118) during endoplasmic reticulum (ER) stress. Despite an AUG codon in the same location, the mouse p53 mRNA does not express the corresponding isoform in either human or mouse-derived cells. High-throughput in-cell RNA structure probing shows that p47 expression is attributed to PERK kinase-dependent structural alterations in the human p53 mRNA, independently of eIF2α. These structural changes do not take place in murine p53 mRNA. Surprisingly, PERK response elements required for the p47 expression are located downstream of the 2nd AUG. The data show that the human p53 mRNA has evolved to respond to PERKmediated regulation of mRNA structures in order to control p47 expression. The findings highlight how p53 mRNA co-evolved with the function of the encoded protein to specify p53-activities under different cellular conditions. |
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| dc.identifier.citation.es.fl_str_mv | Fusée, L, Salomao, N, Ponnuswamy, A [y otros autores]. "The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures". Cell Death & Differentiation. [en línea] 2023, 30(4): 1072–1081. 10 h. DOI: 10.1038/s41418-023-01127-y. |
| dc.identifier.doi.none.fl_str_mv | 10.1038/s41418-023-01127-y |
| dc.identifier.issn.none.fl_str_mv | 1476-5403 |
| dc.identifier.uri.none.fl_str_mv | https://hdl.handle.net/20.500.12008/43176 |
| dc.language.iso.none.fl_str_mv | en eng |
| dc.publisher.es.fl_str_mv | Nature |
| dc.relation.ispartof.es.fl_str_mv | Cell Death & Differentiation, 2023, 30(4): 1072–1081. |
| 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.title.none.fl_str_mv | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| 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 | Cellular stress conditions activate p53-dependent pathways to counteract the inflicted damage. To achieve the required functional diversity, p53 is subjected to numerous post-translational modifications and the expression of isoforms. Little is yet known how p53 has evolved to respond to different stress pathways. The p53 isoform p53/47 (p47 or ΔNp53) is linked to aging and neural degeneration and is expressed in human cells via an alternative cap-independent translation initiation from the 2nd in-frame AUG at codon 40 (+118) during endoplasmic reticulum (ER) stress. Despite an AUG codon in the same location, the mouse p53 mRNA does not express the corresponding isoform in either human or mouse-derived cells. High-throughput in-cell RNA structure probing shows that p47 expression is attributed to PERK kinase-dependent structural alterations in the human p53 mRNA, independently of eIF2α. These structural changes do not take place in murine p53 mRNA. Surprisingly, PERK response elements required for the p47 expression are located downstream of the 2nd AUG. The data show that the human p53 mRNA has evolved to respond to PERKmediated regulation of mRNA structures in order to control p47 expression. The findings highlight how p53 mRNA co-evolved with the function of the encoded protein to specify p53-activities under different cellular conditions. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | COLIBRI_2e8af4fc6cb5ea6c2558ceada73fba5b |
| identifier_str_mv | Fusée, L, Salomao, N, Ponnuswamy, A [y otros autores]. "The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures". Cell Death & Differentiation. [en línea] 2023, 30(4): 1072–1081. 10 h. DOI: 10.1038/s41418-023-01127-y. 1476-5403 10.1038/s41418-023-01127-y |
| 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:20.500.12008/43176 |
| publishDate | 2023 |
| 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 | Fusée L. T. S.Salomao NormanPonnuswamy AnandWang L.López Ferreira Luis Ignacio, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Biología.Chen SaGu XiaolianPolyzoidis StavrosGnanasundram SFahraeus Robin2024-03-19T12:16:26Z2024-03-19T12:16:26Z2023Fusée, L, Salomao, N, Ponnuswamy, A [y otros autores]. "The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures". Cell Death & Differentiation. [en línea] 2023, 30(4): 1072–1081. 10 h. DOI: 10.1038/s41418-023-01127-y.1476-5403https://hdl.handle.net/20.500.12008/4317610.1038/s41418-023-01127-yCellular stress conditions activate p53-dependent pathways to counteract the inflicted damage. To achieve the required functional diversity, p53 is subjected to numerous post-translational modifications and the expression of isoforms. Little is yet known how p53 has evolved to respond to different stress pathways. The p53 isoform p53/47 (p47 or ΔNp53) is linked to aging and neural degeneration and is expressed in human cells via an alternative cap-independent translation initiation from the 2nd in-frame AUG at codon 40 (+118) during endoplasmic reticulum (ER) stress. Despite an AUG codon in the same location, the mouse p53 mRNA does not express the corresponding isoform in either human or mouse-derived cells. High-throughput in-cell RNA structure probing shows that p47 expression is attributed to PERK kinase-dependent structural alterations in the human p53 mRNA, independently of eIF2α. These structural changes do not take place in murine p53 mRNA. Surprisingly, PERK response elements required for the p47 expression are located downstream of the 2nd AUG. The data show that the human p53 mRNA has evolved to respond to PERKmediated regulation of mRNA structures in order to control p47 expression. The findings highlight how p53 mRNA co-evolved with the function of the encoded protein to specify p53-activities under different cellular conditions.Submitted by Pintos Natalia (nataliapintosmvd@gmail.com) on 2024-03-15T19:00:37Z No. of bitstreams: 2 license_rdf: 24251 bytes, checksum: 71ed42ef0a0b648670f707320be37b90 (MD5) 10.1038.s41418-023-01127-y.pdf: 3645742 bytes, checksum: 113b9d464b4e09d8befb670d8171c910 (MD5)Approved for entry into archive by Faget Cecilia (lfaget@fcien.edu.uy) on 2024-03-19T11:57:30Z (GMT) No. of bitstreams: 2 license_rdf: 24251 bytes, checksum: 71ed42ef0a0b648670f707320be37b90 (MD5) 10.1038.s41418-023-01127-y.pdf: 3645742 bytes, checksum: 113b9d464b4e09d8befb670d8171c910 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2024-03-19T12:16:26Z (GMT). No. of bitstreams: 2 license_rdf: 24251 bytes, checksum: 71ed42ef0a0b648670f707320be37b90 (MD5) 10.1038.s41418-023-01127-y.pdf: 3645742 bytes, checksum: 113b9d464b4e09d8befb670d8171c910 (MD5) Previous issue date: 202310 h.application/pdfenengNatureCell Death & Differentiation, 2023, 30(4): 1072–1081.Las 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)The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structuresArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaFusée, L. T. 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- Universidad de la Repúblicafalse |
| spellingShingle | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures Fusée, L. T. S. |
| status_str | publishedVersion |
| title | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| title_full | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| title_fullStr | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| title_full_unstemmed | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| title_short | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| title_sort | The p53 endoplasmic reticulum stress-response pathway evolved in humans but not in mice via PERK-regulated p53 mRNA structures |
| url | https://hdl.handle.net/20.500.12008/43176 |
