Circadian Posttranscriptional Regulation: not only transcription and protein modifications are required for accurate biological clockwork

GARBARINO PICO E; NIETO PS; GUIDO ME

Circadian Rhythms: Biology, Cognition and Disorders

Nova Science Publishers, Inc.

Lugar: New York; Año: 2011; p. 1 - 31

Circadian rhythms are biological variables that oscillate cyclically with a period close to 24 h. These oscillations are generated endogenously by mechanisms driven by biological clocks. The clock at the molecular level is composed of interconnected feedback loops in which a set of genes (clock genes) regulates each other, and also, the expression of an important number of genes (clock controlled genes) in order to regulate a significant number of rhythmic cellular, metabolic, and physiological processes. Importantly, about 3-25% of the transcripts expressed in a given tissue/organ exhibit a circadian oscillation in their levels, explaining how clocks regulate biochemical and cellular processes. The current clock model in Eukaryotes involves at least two interconnected transcriptional feedback loops. Additionally, the post-translational modifications regulating translocations, interactions, and stability of clock proteins, have been also shown to be an important component of the clock mechanism. Just in recent years it has become increasingly clear that posttranscriptional processes are also important for understanding the clock functioning and kinetics. Presently, we know that several posttranscriptional events participate in the clock mechanism itself, and in the control of circadian gene expression. These events include the regulation of splicing, polyadenylation, mRNA stability, and translation. RNA-binding proteins (RBPs) and microRNAs (miRNAs) have been reported to be implicated in most of these processes, and have emerged as important players in controlling gene expression. Importantly, the perturbation of some rhythmic posttranscriptional events has been shown to cause metabolic syndromes and other diseases. The aim of this chapter is to shed light on the role that posttranscriptional regulation plays in the molecular clock mechanism, as well as in the modulation of circadian gene expression.