Effect of a RNA-binding protein (RBP) on the dynamics of the Molecular Circadian Clock.

NIETO PS; REVELLI JA; GARBARINO PICO E; GUIDO ME; TAMARIT FA

Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2012

Most living beings exhibit physiological and behavioural circadian
rhythms with an endogenous period of about 24 h, which can be
synchronized and anticipate to periodic cues. At molecular level,
the circadian timekeeping mechanism is driven by a set of genes,
called clock genes which interact in oscillatory transcriptionaltranslational
networks within cells. The majority of mammalian
cells have a circadian molecular clock and they are coordinated by
a master circadian pacemaker in the mammalian brain called the
suprachiasmatic nucleus (SCN).
Numerous observations have revealed the importance of posttranscriptional
regulation on circadian gene expression
(Garbarino-Pico and Green 2007) and recent studies have
demonstrated that several clock genes are post-translationally
regulated by RBPs (reviewed in Lowrey and Takahashi 2011 and
Garbarino-Pico et al., 2011) .
In the present work we show numerical results obtained with a
mathematical model for the circadian molecular clock, which
includes the regulation of Per mRNA translation by a RBP. We
found that depending on the values of the RBP-associated
parameters, the period and amplitude of the oscillator are affected.
The magnitude of those changes depend on whether the repression
of transcription is assumed as a cooperative or non-cooperative
event.