Cis to trans: small ORF functions emerging through evolution

Hundreds of thousands of small open reading frames (smORFs) of less than 100 codons exist in every genome, especially in long noncoding RNAs (lncRNAs) and in the 5′ leaders of mRNAs. smORFs are often discarded as nonfunctional, but ribosomal profiling (RiboSeq) reveals that thousands are translated,...

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Detalles Bibliográficos
Autores: Baena-Angulo, Casimiro, Platero, Ana Isabel, Couso, Juan Pablo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/393540
Acceso en línea:http://hdl.handle.net/10261/393540
Access Level:acceso abierto
Palabra clave:Small ORFs
Short ORFs
SmORF-encoded peptides
Microproteins
lncRNAs
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spelling Cis to trans: small ORF functions emerging through evolutionBaena-Angulo, CasimiroPlatero, Ana IsabelCouso, Juan PabloSmall ORFsShort ORFsSmORF-encoded peptidesMicroproteinslncRNAsHundreds of thousands of small open reading frames (smORFs) of less than 100 codons exist in every genome, especially in long noncoding RNAs (lncRNAs) and in the 5′ leaders of mRNAs. smORFs are often discarded as nonfunctional, but ribosomal profiling (RiboSeq) reveals that thousands are translated, while characterised smORF functions have risen from anecdotal to identifiable trends: smORFs can either have a cis-noncoding regulatory function (involving low translation of nonfunctional peptides) or full coding function mediated by robustly translated peptides, often having cellular and physiological roles as membrane-associated regulators of canonical proteins. The evolutionary context reveals that many smORFs represent new genes emerging de novo from noncoding sequences. We suggest a mechanism for this process, where cis-noncoding smORF functions provide niches for the subsequent evolution of full peptide functions.This work was funded by grants from the Spanish Ministerio de Ciencia to J.P.C. (refs. PID2022-141831NB-I00/AEI/10.13039/501100011033/FEDER, UE and EUR2022-134063), the project CEX2020-001088-M, funded by the Programme Grant MCIN/AEI/10.13039/501100011033O and an FPI fellowship (PRE2019-091601) associated with Programme Grant MDM-2016-0687 to C.B.A.With funding from the Spanish government through the ‘María de Maeztu Unit of Excelence’ accreditation (CEX2020-001088-M).With funding from the Spanish government through the ‘María de Maeztu Unit of Excelence’ accreditation (MDM-2016-0687)Peer reviewedCell PressMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/393540reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-141831NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2020-001088-Minfo:eu-repo/grantAgreement/AEI//PRE2019-091601info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/MDM-2016-0687The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.tig.2024.10.012https://doi.org/10.1016/j.tig.2024.10.012Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3935402026-05-22T06:33:51Z
dc.title.none.fl_str_mv Cis to trans: small ORF functions emerging through evolution
title Cis to trans: small ORF functions emerging through evolution
spellingShingle Cis to trans: small ORF functions emerging through evolution
Baena-Angulo, Casimiro
Small ORFs
Short ORFs
SmORF-encoded peptides
Microproteins
lncRNAs
title_short Cis to trans: small ORF functions emerging through evolution
title_full Cis to trans: small ORF functions emerging through evolution
title_fullStr Cis to trans: small ORF functions emerging through evolution
title_full_unstemmed Cis to trans: small ORF functions emerging through evolution
title_sort Cis to trans: small ORF functions emerging through evolution
dc.creator.none.fl_str_mv Baena-Angulo, Casimiro
Platero, Ana Isabel
Couso, Juan Pablo
author Baena-Angulo, Casimiro
author_facet Baena-Angulo, Casimiro
Platero, Ana Isabel
Couso, Juan Pablo
author_role author
author2 Platero, Ana Isabel
Couso, Juan Pablo
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Small ORFs
Short ORFs
SmORF-encoded peptides
Microproteins
lncRNAs
topic Small ORFs
Short ORFs
SmORF-encoded peptides
Microproteins
lncRNAs
description Hundreds of thousands of small open reading frames (smORFs) of less than 100 codons exist in every genome, especially in long noncoding RNAs (lncRNAs) and in the 5′ leaders of mRNAs. smORFs are often discarded as nonfunctional, but ribosomal profiling (RiboSeq) reveals that thousands are translated, while characterised smORF functions have risen from anecdotal to identifiable trends: smORFs can either have a cis-noncoding regulatory function (involving low translation of nonfunctional peptides) or full coding function mediated by robustly translated peptides, often having cellular and physiological roles as membrane-associated regulators of canonical proteins. The evolutionary context reveals that many smORFs represent new genes emerging de novo from noncoding sequences. We suggest a mechanism for this process, where cis-noncoding smORF functions provide niches for the subsequent evolution of full peptide functions.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/393540
url http://hdl.handle.net/10261/393540
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-141831NB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2020-001088-M
info:eu-repo/grantAgreement/AEI//PRE2019-091601
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/MDM-2016-0687
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1016/j.tig.2024.10.012
https://doi.org/10.1016/j.tig.2024.10.012

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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