Effects of different per translational kinetics on the dynamics of a core circadian clock model

PLoS One. 2015 Jan 21;10(1):e0115067. doi: 10.1371/journal.pone.0115067. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Clocks / physiology*
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Drosophila melanogaster
  • Gene Expression Regulation / physiology*
  • Models, Biological*
  • Period Circadian Proteins / biosynthesis*
  • Period Circadian Proteins / genetics
  • Protein Biosynthesis / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics

Substances

  • Drosophila Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • RNA, Messenger

Grants and funding

The authors have no support or funding to report.