hnRNP Q and PTB modulate the circadian oscillation of mouse Rev-erb alpha via IRES-mediated translation

Abstract

The physiological and behavioral circadian rhythms of most creatures are controlled by a harmony of functional relationships between clock genes. In mammals, several core clock genes show rhythmic profiles of their mRNA and protein expression. Among them, Rev-erb alpha functions as a transcriptional repressor, affecting expression patterns of other clock genes. For the continuous and robust oscillation of the molecular clock system, the levels of Rev-erb alpha protein are expected to be tightly regulated with the correct timing. Here, we demonstrate that Rev-erb alpha has an internal ribosomal entry site (IRES) in its 5' untranslated region. Furthermore, we demonstrate that heterogeneous nuclear ribonucleoprotein Q and polypyrimidine tract-binding protein (PTB) modulate the IRES-mediated translation of Rev-erb alpha. We suggest that the rhythmic binding affinity of hnRNP Q to the Rev-erb alpha IRES and the change in PTB cytosolic levels lead to maintenance of the oscillation profile of the Rev-erb alpha protein.