Stress Granules are circadianly regulated

GARBARINO PICO E; GUIDO ME

Congreso; Latin American Symposium on Chronobiology; 2013

It has been proposed that avoiding UV radiation may have been one of the main selection forces that gave rise to circadian rhythms. Indeed, stress response is circadian modulated in several experimental models. Numerous stress-types induces the formation of microscopically visible cytoplasmic ribonucleoprotein aggregated called stress granules (SG). SG are mainly formed by stalled translation initiation complexes. Since a number of SG components display circadian rhythms, we hypothesized that SG could be temporarily regulated. We analyzed SG by ICC with an anti-eIF3 antibody in synchronized NIH3T3 cell cultures. SG were induced with arsenite (oxidative stress). We found that SG number and signal intensity present temporal changes. Area and perimeter showed only modest variations. The expression of eIF3 did not change. We found no changes in phosphorylated eIF2alpha, a protein involved in SG assembly. Then we analyzed by RT-qPCR the temporal expression of several RNA-binding proteins that are in SG and could be involved in the temporal changes observed. Interesting, Tia1, Brf1, hnRNPQ, and Lark transcripts presented temporal changes in their levels. TIA1 protein has been implicated in SG assembly; we found that its levels also oscillate. LARK, which regulates the translation of the clock protein PER1, also presented temporal variations and induction by stress. Our results show that SG are temporarily regulated and may be involved in the circadian regulation of stress response.