Protein tandem repeats that produce frameshifts can generate new structural states and functions

Autores
Osmanli, Zarifa; Aldrian, Gudrun; Leclercq, Jeremy; Falgarone, Theo; Gomez Bergna, Santiago Manuel; Prada Gori, Denis Nihuel; Oleinikov, Andrew V.; Shahmuradov, Ilham; Kajava, Andrey V.
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The genetic code uses three-nucleotide units to encode each amino acid inproteins. Insertions or deletions of nucleotides not divisible by three shiftthe reading frames, resulting in significantly different protein sequences.These events are disruptive but can also create variability important forevolution. Previous studies suggested that the genetic code and genesequences evolve to minimize frameshift effects, maintaining similar physicochemicalproperties to their reference proteins. Here, we focused on tandemrepeat sequences, known as frameshift hotspots. Using cutting-edgebioinformatics tools, we compared reference and frameshifted proteinsequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes.We showed that, in contrast to the general tendency, frameshiftswithin these regions, especially with short repeats, lead to a significantincrease in hydrophobicity and arginine content. Additionally, the frameshifts,particularly in short tandem repeats, rearrange transmembraneregions, potentially converting soluble proteins into membrane proteinsand vice versa. Given their occurrence in rapidly evolving, essential proteins,such changes may promote rapid adaptability. Our large-scale ALPHAFOLDmodeling suggested that frameshift events can generate novelstructures and functions, enabling the synthesis of multiple protein variantswithin the same coding region. Overall, frameshifts cause more drasticchanges in tandem repeat sequences compared to non-repetitive sequencesand therefore can be a primary cause of altered functions, cellular localization,and the development of various pathologies.
Fil: Osmanli, Zarifa. Centre National de la Recherche Scientifique; Francia
Fil: Aldrian, Gudrun. Centre National de la Recherche Scientifique; Francia
Fil: Leclercq, Jeremy. Centre National de la Recherche Scientifique; Francia
Fil: Falgarone, Theo. Centre National de la Recherche Scientifique; Francia
Fil: Gomez Bergna, Santiago Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Prada Gori, Denis Nihuel. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Oleinikov, Andrew V.. Florida Atlantic University (fau);
Fil: Shahmuradov, Ilham. No especifíca;
Fil: Kajava, Andrey V.. Centre National de la Recherche Scientifique; Francia
Materia
ALPHAFOLD
CODON USAGE
FRAMESHIFTING
LARGE-SCALE ANALYSIS
TANDEM REPEAT PROTEINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/282354
Acceder
id CONICETDig_d6d25984ed4705388adcc71134d5a7ad
oai_identifier_str oai:ri.conicet.gov.ar:11336/282354
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Protein tandem repeats that produce frameshifts can generate new structural states and functionsOsmanli, ZarifaAldrian, GudrunLeclercq, JeremyFalgarone, TheoGomez Bergna, Santiago ManuelPrada Gori, Denis NihuelOleinikov, Andrew V.Shahmuradov, IlhamKajava, Andrey V.ALPHAFOLDCODON USAGEFRAMESHIFTINGLARGE-SCALE ANALYSISTANDEM REPEAT PROTEINShttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1The genetic code uses three-nucleotide units to encode each amino acid inproteins. Insertions or deletions of nucleotides not divisible by three shiftthe reading frames, resulting in significantly different protein sequences.These events are disruptive but can also create variability important forevolution. Previous studies suggested that the genetic code and genesequences evolve to minimize frameshift effects, maintaining similar physicochemicalproperties to their reference proteins. Here, we focused on tandemrepeat sequences, known as frameshift hotspots. Using cutting-edgebioinformatics tools, we compared reference and frameshifted proteinsequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes.We showed that, in contrast to the general tendency, frameshiftswithin these regions, especially with short repeats, lead to a significantincrease in hydrophobicity and arginine content. Additionally, the frameshifts,particularly in short tandem repeats, rearrange transmembraneregions, potentially converting soluble proteins into membrane proteinsand vice versa. Given their occurrence in rapidly evolving, essential proteins,such changes may promote rapid adaptability. Our large-scale ALPHAFOLDmodeling suggested that frameshift events can generate novelstructures and functions, enabling the synthesis of multiple protein variantswithin the same coding region. Overall, frameshifts cause more drasticchanges in tandem repeat sequences compared to non-repetitive sequencesand therefore can be a primary cause of altered functions, cellular localization,and the development of various pathologies.Fil: Osmanli, Zarifa. Centre National de la Recherche Scientifique; FranciaFil: Aldrian, Gudrun. Centre National de la Recherche Scientifique; FranciaFil: Leclercq, Jeremy. Centre National de la Recherche Scientifique; FranciaFil: Falgarone, Theo. Centre National de la Recherche Scientifique; FranciaFil: Gomez Bergna, Santiago Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; ArgentinaFil: Prada Gori, Denis Nihuel. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Oleinikov, Andrew V.. Florida Atlantic University (fau);Fil: Shahmuradov, Ilham. No especifíca;Fil: Kajava, Andrey V.. Centre National de la Recherche Scientifique; FranciaWiley Blackwell Publishing, Inc2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/282354Osmanli, Zarifa; Aldrian, Gudrun; Leclercq, Jeremy; Falgarone, Theo; Gomez Bergna, Santiago Manuel; et al.; Protein tandem repeats that produce frameshifts can generate new structural states and functions; Wiley Blackwell Publishing, Inc; Febs Journal; 293; 3; 9-2025; 842-8581742-464XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.70273info:eu-repo/semantics/altIdentifier/doi/10.1111/febs.70273info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-11T11:57:49Zoai:ri.conicet.gov.ar:11336/282354instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-03-11 11:57:49.228CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protein tandem repeats that produce frameshifts can generate new structural states and functions
title Protein tandem repeats that produce frameshifts can generate new structural states and functions
spellingShingle Protein tandem repeats that produce frameshifts can generate new structural states and functions
Osmanli, Zarifa
ALPHAFOLD
CODON USAGE
FRAMESHIFTING
LARGE-SCALE ANALYSIS
TANDEM REPEAT PROTEINS
title_short Protein tandem repeats that produce frameshifts can generate new structural states and functions
title_full Protein tandem repeats that produce frameshifts can generate new structural states and functions
title_fullStr Protein tandem repeats that produce frameshifts can generate new structural states and functions
title_full_unstemmed Protein tandem repeats that produce frameshifts can generate new structural states and functions
title_sort Protein tandem repeats that produce frameshifts can generate new structural states and functions
dc.creator.none.fl_str_mv Osmanli, Zarifa
Aldrian, Gudrun
Leclercq, Jeremy
Falgarone, Theo
Gomez Bergna, Santiago Manuel
Prada Gori, Denis Nihuel
Oleinikov, Andrew V.
Shahmuradov, Ilham
Kajava, Andrey V.
author Osmanli, Zarifa
author_facet Osmanli, Zarifa
Aldrian, Gudrun
Leclercq, Jeremy
Falgarone, Theo
Gomez Bergna, Santiago Manuel
Prada Gori, Denis Nihuel
Oleinikov, Andrew V.
Shahmuradov, Ilham
Kajava, Andrey V.
author_role author
author2 Aldrian, Gudrun
Leclercq, Jeremy
Falgarone, Theo
Gomez Bergna, Santiago Manuel
Prada Gori, Denis Nihuel
Oleinikov, Andrew V.
Shahmuradov, Ilham
Kajava, Andrey V.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALPHAFOLD
CODON USAGE
FRAMESHIFTING
LARGE-SCALE ANALYSIS
TANDEM REPEAT PROTEINS
topic ALPHAFOLD
CODON USAGE
FRAMESHIFTING
LARGE-SCALE ANALYSIS
TANDEM REPEAT PROTEINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The genetic code uses three-nucleotide units to encode each amino acid inproteins. Insertions or deletions of nucleotides not divisible by three shiftthe reading frames, resulting in significantly different protein sequences.These events are disruptive but can also create variability important forevolution. Previous studies suggested that the genetic code and genesequences evolve to minimize frameshift effects, maintaining similar physicochemicalproperties to their reference proteins. Here, we focused on tandemrepeat sequences, known as frameshift hotspots. Using cutting-edgebioinformatics tools, we compared reference and frameshifted proteinsequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes.We showed that, in contrast to the general tendency, frameshiftswithin these regions, especially with short repeats, lead to a significantincrease in hydrophobicity and arginine content. Additionally, the frameshifts,particularly in short tandem repeats, rearrange transmembraneregions, potentially converting soluble proteins into membrane proteinsand vice versa. Given their occurrence in rapidly evolving, essential proteins,such changes may promote rapid adaptability. Our large-scale ALPHAFOLDmodeling suggested that frameshift events can generate novelstructures and functions, enabling the synthesis of multiple protein variantswithin the same coding region. Overall, frameshifts cause more drasticchanges in tandem repeat sequences compared to non-repetitive sequencesand therefore can be a primary cause of altered functions, cellular localization,and the development of various pathologies.
Fil: Osmanli, Zarifa. Centre National de la Recherche Scientifique; Francia
Fil: Aldrian, Gudrun. Centre National de la Recherche Scientifique; Francia
Fil: Leclercq, Jeremy. Centre National de la Recherche Scientifique; Francia
Fil: Falgarone, Theo. Centre National de la Recherche Scientifique; Francia
Fil: Gomez Bergna, Santiago Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Biotecnología y Biología Molecular. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Biotecnología y Biología Molecular; Argentina
Fil: Prada Gori, Denis Nihuel. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Oleinikov, Andrew V.. Florida Atlantic University (fau);
Fil: Shahmuradov, Ilham. No especifíca;
Fil: Kajava, Andrey V.. Centre National de la Recherche Scientifique; Francia
description The genetic code uses three-nucleotide units to encode each amino acid inproteins. Insertions or deletions of nucleotides not divisible by three shiftthe reading frames, resulting in significantly different protein sequences.These events are disruptive but can also create variability important forevolution. Previous studies suggested that the genetic code and genesequences evolve to minimize frameshift effects, maintaining similar physicochemicalproperties to their reference proteins. Here, we focused on tandemrepeat sequences, known as frameshift hotspots. Using cutting-edgebioinformatics tools, we compared reference and frameshifted proteinsequences within tandem repeats across 50 prokaryotic and eukaryotic proteomes.We showed that, in contrast to the general tendency, frameshiftswithin these regions, especially with short repeats, lead to a significantincrease in hydrophobicity and arginine content. Additionally, the frameshifts,particularly in short tandem repeats, rearrange transmembraneregions, potentially converting soluble proteins into membrane proteinsand vice versa. Given their occurrence in rapidly evolving, essential proteins,such changes may promote rapid adaptability. Our large-scale ALPHAFOLDmodeling suggested that frameshift events can generate novelstructures and functions, enabling the synthesis of multiple protein variantswithin the same coding region. Overall, frameshifts cause more drasticchanges in tandem repeat sequences compared to non-repetitive sequencesand therefore can be a primary cause of altered functions, cellular localization,and the development of various pathologies.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/282354
Osmanli, Zarifa; Aldrian, Gudrun; Leclercq, Jeremy; Falgarone, Theo; Gomez Bergna, Santiago Manuel; et al.; Protein tandem repeats that produce frameshifts can generate new structural states and functions; Wiley Blackwell Publishing, Inc; Febs Journal; 293; 3; 9-2025; 842-858
1742-464X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/282354
identifier_str_mv Osmanli, Zarifa; Aldrian, Gudrun; Leclercq, Jeremy; Falgarone, Theo; Gomez Bergna, Santiago Manuel; et al.; Protein tandem repeats that produce frameshifts can generate new structural states and functions; Wiley Blackwell Publishing, Inc; Febs Journal; 293; 3; 9-2025; 842-858
1742-464X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.70273
info:eu-repo/semantics/altIdentifier/doi/10.1111/febs.70273
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.977003

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