hnRNP Q mediates a phase-dependent translation-coupled mRNA decay of mouse Period3

Abstract

Daily mRNA oscillations of circadian clock genes largely depend on transcriptional regulation. However, several lines of evidence highlight the critical role of post-transcriptional regulation in the oscillations of circadian mRNA oscillations. Clearly, variations in the mRNA decay rate lead to changes in the cycling profiles. However, the mechanisms controlling the mRNA stability of clock genes are not fully understood. Here we demonstrate that the turnover rate of mouse Period3 (mPer3) mRNA is dramatically changed in a circadian phase-dependent manner. Furthermore, the circadian regulation of mPer3 mRNA stability requires the cooperative function of 5′- and 3′-untranslated regions (UTRs). Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) binds to both 5′- and 3′-UTR and triggers enhancement of translation and acceleration of mRNA decay. We propose the phase-dependent translation coupled mRNA decay mediated by hnRNP Q as a new regulatory mechanism of the rhythmically regulated decay of mPer3 mRNA.

Pigment-Dispersing Factor Modulates Pheromone Production in Clock Cells that Influence Mating in Drosophila

“…However, given that the desat1-luc transgene contains the promotor and the 5' untranslated region (5'UTR) of the desat1-RE transcript, it is plausible that the expression of the luciferase protein is subject to additional regulatory influences which are not observable when measuring clock gene and desat1 transcription alone. Mechanisms of post-transcriptional regulation mediated by the 5'UTR, such as transcript stability and translation, are involved in the circadian regulation of clock-controlled genes in plants and mammals (Kim et al, 2011; Kim et al 2007; Ovadia et al, 2010). Similarly, post-transcriptional regulation via micro-RNAs plays a role in the circadian biology of Drosophila (Kadener et al, 2009), and although there are no published examples of such regulation through interactions with the 5'UTR such a mechanism is possible.…”

Post‐transcriptional regulation of gene expression in neural stem cells

“…Multiple post‐transcriptional regulatory mechanisms may occur simultaneously, and in such cases, these processes may be interconnected and coordinated. mRNA localization, stability, or translation can be influenced by alternative polyadenylation . The detailed roles of post‐transcriptional mechanisms in NSPC fate decisions remain to be discovered.…”

Ribonucleoprotein Complexes That Control Circadian Clocks

“…In mammals, hnRNP Q, hnRNP L and hnRNP R bind to AANAT mRNA 3′UTR region and destabilize the transcripts; hnRNP Q, hnRNP L and hnRNP R are necessary for maintaining the normal rhythm of melatonin [117]. hnRNP Q also binds to both the mRNA 5′ and 3′ UTR regions of mouse clock gene Period3 , to regulate the translation and mRNA decay respectively [118]. There are several known pathways that control the mRNA turnover, which are 3′→5′ exonucleolytic decay, 5′→3′ exonucleolytic decay and endonuclease cleavage, respectively [112,115].…”