MicroRNA-mediated regulation in the mammalian circadian rhythm

Journal of Theoretical Biology
Kaihui Liu, Ruiqi Wang

Abstract

Mammalian circadian rhythms have been extensively studied for many years and many computational models have been presented. Most of the circadian rhythms are based on interlocked positive and negative feedback loops involving coding regions of some 'clock' genes. Recent works have implicated that microRNAs (miRNAs) may play crucial roles in modulating the circadian clock. Here we develop a computational model involving four genes, Per, Cry, Bmal1, and Clock, and two miRNAs, miRNA-219 and miRNA-132, to show their post-transcriptional roles in the modulation of the circadian rhythm. The model is based on experimental observations, by which the miRNAs are incorporated into a classic model including only coding genes. In agreement with experimental observations, the model predicts that miRNA-mediated regulation plays critical roles in modulating the circadian clock. In addition, parameter sensitivity analysis indicates that the period of circadian rhythm with miRNA-mediated regulation is more insensitive to perturbations, showing that the miRNA-mediated regulation can enhance the robustness of the circadian rhythms. This study may help us understand the microRNA-mediated regulation in the mammalian circadian rhythm more clearly.

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Citations

Nov 13, 2012·Journal of Molecular Biology·Neel Mehta, Hai-Ying M Cheng
Jul 3, 2013·Environmental and Molecular Mutagenesis·Fengqin ShiYong Zhu
Mar 1, 2016·Journal of Hepatology·Yuyan HanGianfranco Alpini
Oct 6, 2015·Worm·Priscilla M Van Wynsberghe, Amy E Pasquinelli
Jul 4, 2013·Journal of Theoretical Biology·J M González-Miranda
May 19, 2017·Molecular Neurobiology·Utpal BhadraManika Pal-Bhadra
May 31, 2018·American Journal of Physiology. Renal Physiology·Roel BijkerkAnton Jan van Zonneveld
Jul 30, 2015·Oncotarget·David Z Kochan, Olga Kovalchuk
Oct 3, 2019·Physical Review. E·Paula S Nieto, C A Condat
Aug 24, 2018·The Journal of Experimental Biology·Jenni M Prokkola, Mikko Nikinmaa
Sep 10, 2020·International Journal of Molecular Sciences·Abdelnaby KhalyfaDavid Gozal
Oct 11, 2014·Biochemistry·Shihoko Kojima, Carla B Green

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