Department of Life Science, Division of Molecular and Life Science, School of Interdisciplinary Bioscience and Bioengineering and Division of Integrative Bioscience & Biotechnology, Pohang University of Science and Technology, Pohang, Gyeong-Buk, 790-784, Republic of Korea.
Nucleic Acids Res. 2011 Nov 1;39(20):8901-14. doi: 10.1093/nar/gkr605. Epub 2011 Jul 23.
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.
生物钟基因的日常 mRNA 波动在很大程度上取决于转录调控。然而,有几条证据强调了在生物钟 mRNA 波动的转录后调控的关键作用。显然,mRNA 降解率的变化导致了循环谱的变化。然而,控制生物钟基因 mRNA 稳定性的机制尚不完全清楚。在这里,我们证明了小鼠 Period3(mPer3)mRNA 的周转率以昼夜节律相位依赖的方式发生显著变化。此外,mPer3 mRNA 稳定性的昼夜节律调节需要 5'-和 3'-非翻译区(UTR)的协同功能。异质核核糖核蛋白 Q(hnRNP Q)结合 5'-和 3'-UTR,并触发翻译增强和 mRNA 降解加速。我们提出了 hnRNP Q 介导的与翻译偶联的 mRNA 衰减的相位依赖性,作为 mPer3 mRNA 节律性调节衰减的新调节机制。