Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model

Autores
Nieto, Paula Sofia; Revelli, Jorge Alberto; Garbarino Pico, Eduardo; Condat, Carlos; Guido, Mario Eduardo; Tamarit, Francisco
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.
Fil: Nieto, Paula Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Fil: Revelli, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Fil: Garbarino Pico, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina
Fil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Fil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina
Fil: Tamarit, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Materia
CIRCADIAN CLOCKS
PER TRANSLATION
MATHEMATICAL MODELS
POST-TRANSCRIPTIONAL MODULATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10632

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network_name_str CONICET Digital (CONICET)
spelling Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock modelNieto, Paula SofiaRevelli, Jorge AlbertoGarbarino Pico, EduardoCondat, CarlosGuido, Mario EduardoTamarit, FranciscoCIRCADIAN CLOCKSPER TRANSLATIONMATHEMATICAL MODELSPOST-TRANSCRIPTIONAL MODULATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.Fil: Nieto, Paula Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Revelli, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Garbarino Pico, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; ArgentinaFil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; ArgentinaFil: Tamarit, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaPublic Library Of Science2015-01-21info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10632Nieto, Paula Sofia; Revelli, Jorge Alberto; Garbarino Pico, Eduardo; Condat, Carlos; Guido, Mario Eduardo; et al.; Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model; Public Library Of Science; Plos One; 10; 1; 21-1-2015; 1-271932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0115067info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25607544/info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115067info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:52:30Zoai:ri.conicet.gov.ar:11336/10632instacron: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:34982025-09-29 09:52:30.45CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
title Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
spellingShingle Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
Nieto, Paula Sofia
CIRCADIAN CLOCKS
PER TRANSLATION
MATHEMATICAL MODELS
POST-TRANSCRIPTIONAL MODULATION
title_short Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
title_full Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
title_fullStr Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
title_full_unstemmed Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
title_sort Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model
dc.creator.none.fl_str_mv Nieto, Paula Sofia
Revelli, Jorge Alberto
Garbarino Pico, Eduardo
Condat, Carlos
Guido, Mario Eduardo
Tamarit, Francisco
author Nieto, Paula Sofia
author_facet Nieto, Paula Sofia
Revelli, Jorge Alberto
Garbarino Pico, Eduardo
Condat, Carlos
Guido, Mario Eduardo
Tamarit, Francisco
author_role author
author2 Revelli, Jorge Alberto
Garbarino Pico, Eduardo
Condat, Carlos
Guido, Mario Eduardo
Tamarit, Francisco
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CIRCADIAN CLOCKS
PER TRANSLATION
MATHEMATICAL MODELS
POST-TRANSCRIPTIONAL MODULATION
topic CIRCADIAN CLOCKS
PER TRANSLATION
MATHEMATICAL MODELS
POST-TRANSCRIPTIONAL MODULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.
Fil: Nieto, Paula Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Fil: Revelli, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Fil: Garbarino Pico, Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina
Fil: Condat, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
Fil: Guido, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones En Química Biológica de Córdoba (p); Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Quimica Biológica; Argentina
Fil: Tamarit, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto de Física "enrique Gaviola"; Argentina. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina
description Living beings display self-sustained daily rhythms in multiple biological processes, which persist in the absence of external cues since they are generated by endogenous circadian clocks. The period (per) gene is a central player within the core molecular mechanism for keeping circadian time in most animals. Recently, the modulation PER translation has been reported, both in mammals and flies, suggesting that translational regulation of clock components is important for the proper clock gene expression and molecular clock performance. Because translational regulation ultimately implies changes in the kinetics of translation and, therefore, in the circadian clock dynamics, we sought to study how and to what extent the molecular clock dynamics is affected by the kinetics of PER translation. With this objective, we used a minimal mathematical model of the molecular circadian clock to qualitatively characterize the dynamical changes derived from kinetically different PER translational mechanisms. We found that the emergence of self-sustained oscillations with characteristic period, amplitude, and phase lag (time delays) between per mRNA and protein expression depends on the kinetic parameters related to PER translation. Interestingly, under certain conditions, a PER translation mechanism with saturable kinetics introduces longer time delays than a mechanism ruled by a first-order kinetics. In addition, the kinetic laws of PER translation significantly changed the sensitivity of our model to parameters related to the synthesis and degradation of per mRNA and PER degradation. Lastly, we found a set of parameters, with realistic values, for which our model reproduces some experimental results reported recently for Drosophila melanogaster and we present some predictions derived from our analysis.
publishDate 2015
dc.date.none.fl_str_mv 2015-01-21
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/10632
Nieto, Paula Sofia; Revelli, Jorge Alberto; Garbarino Pico, Eduardo; Condat, Carlos; Guido, Mario Eduardo; et al.; Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model; Public Library Of Science; Plos One; 10; 1; 21-1-2015; 1-27
1932-6203
url http://hdl.handle.net/11336/10632
identifier_str_mv Nieto, Paula Sofia; Revelli, Jorge Alberto; Garbarino Pico, Eduardo; Condat, Carlos; Guido, Mario Eduardo; et al.; Effects of different PER translational kinetics on the dynamics of a Core Circadian Clock model; Public Library Of Science; Plos One; 10; 1; 21-1-2015; 1-27
1932-6203
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115067
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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