Temporal regulation of stress granules by circadian clocks and other mechanism.

MALCOLM M; GUIDO ME; RÍOS MN; GARBARINO PICO E; SAAD LF

Córdoba

Congreso; 52 Reunión Anual de la SAIB; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Stress granules (SGs) are microscopically visible foci formed in response to stress by assemblies of untranslating messenger ribonucleoproteins from mRNAs stalled in translation initiation. Since a number of SG components display circadian rhythms, we had hypothesized that these mRNA granules could be circadianly regulated. Indeed, we have previously shown that SGs induced by oxidative stress display daily changes in their number and size in synchronized NIH3T3 cultures. In order to establish whether the oscillations observed were truly circadian rhythms, we performed similar experiments in clock defective cells. We utilized fibroblasts from knockout or double knockout mice for different clock genes: Bmal1, Per1/2 and Cry1/2 and their corresponding wt controls. In all cases we found significant changes through time in the number, area, and signal intensity of eIF3 immunolabeled SGs in synchronized cultures. However the period, amplitude, and phase of the oscillations were different in each genotype. Since these parameters are altered in cells without a functional circadian clock, we concluded that the described oscillations are modulated by this timing mechanism but also for some other metabolic driver. It has been reported redox rhythms in several systems controlled by mechanisms different from the canonical clock, which could be responsible of the oscillations we observed.