title: Effects of different per translational kinetics on the dynamics of a core circadian clock model.
abstract: 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.
authors.affiliation: Instituto de Física Enrique Gaviola (IFEG-CONICET) and Facultad de Matemática, Astronomía y Física (FaMAF), Universidad Nacional de Córdoba (UNC). Ciudad Universitaria, CP:X5000HUA Córdoba, Argentina.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Nieto
authors.affiliation: Instituto de Física Enrique Gaviola (IFEG-CONICET) and Facultad de Matemática, Astronomía y Física (FaMAF), Universidad Nacional de Córdoba (UNC). Ciudad Universitaria, CP:X5000HUA Córdoba, Argentina.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Revelli
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC). Ciudad Universitaria, CP:X5000HUA Córdoba, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Garbarino-Pico
authors.affiliation: Instituto de Física Enrique Gaviola (IFEG-CONICET) and Facultad de Matemática, Astronomía y Física (FaMAF), Universidad Nacional de Córdoba (UNC). Ciudad Universitaria, CP:X5000HUA Córdoba, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Condat
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC-CONICET) and Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC). Ciudad Universitaria, CP:X5000HUA Córdoba, Argentina.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Guido
authors.affiliation: Instituto de Física Enrique Gaviola (IFEG-CONICET) and Facultad de Matemática, Astronomía y Física (FaMAF), Universidad Nacional de Córdoba (UNC). Ciudad Universitaria, CP:X5000HUA Córdoba, Argentina.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tamarit
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation / Q000502:physiology*; D008954:Models, Biological; D056950:Period Circadian Proteins / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D012333:RNA, Messenger