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

NIETO, P.S.; REVELLI, J.A.; GARBARINO-PICO, E.; GUIDO, M. E.; TAMARIT, F.A.

Mendoza

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

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Most living beings exhibit physiological and behavioural circadianrhythms with an endogenous period of about 24 h, which can besynchronized 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 transcriptionaltranslationalnetworks within cells. The majority of mammaliancells have a circadian molecular clock and they are coordinated bya master circadian pacemaker in the mammalian brain called thesuprachiasmatic nucleus (SCN).Numerous observations have revealed the importance of posttranscriptionalregulation on circadian gene expression(Garbarino-Pico and Green 2007) and recent studies havedemonstrated that several clock genes are post-translationallyregulated by RBPs (reviewed in Lowrey and Takahashi 2011 andGarbarino-Pico et al., 2011) .In the present work we show numerical results obtained with amathematical model for the circadian molecular clock, whichincludes the regulation of Per mRNA translation by a RBP. Wefound that depending on the values of the RBP-associatedparameters, the period and amplitude of the oscillator are affected.The magnitude of those changes depend on whether the repressionof transcription is assumed as a cooperative or non-cooperativeevent.