Koichiro Uriu, Juan P Hernandez-Sanchez, Shihoko Kojima
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Impacts of the feedback loop between sense-antisense RNAs in regulating circadian rhythms.
Antisense transcripts are a unique group of non-coding RNAs and play regulatory roles in a variety of biological processes, including circadian rhythms. Per2AS is an antisense transcript to the sense core clock gene Period2 (Per2) in mouse and its expression is rhythmic and antiphasic to Per2. To understand the impact of Per2AS-Per2 interaction, we developed a new mathematical model that mechanistically described the mutually repressive relationship between Per2 and Per2AS. This mutual repression can regulate both amplitude and period of circadian oscillation by affecting a negative feedback regulation of Per2. Simulations from this model also fit with experimental observations that could not be fully explained by our previous model. Our revised model can not only serve as a foundation to build more detailed models to better understand the impact of Per2AS-Per2 interaction in the future, but also be used to analyze other sense-antisense RNA pairs that mutually repress each other.
期刊介绍:
npj Systems Biology and Applications is an online Open Access journal dedicated to publishing the premier research that takes a systems-oriented approach. The journal aims to provide a forum for the presentation of articles that help define this nascent field, as well as those that apply the advances to wider fields. We encourage studies that integrate, or aid the integration of, data, analyses and insight from molecules to organisms and broader systems. Important areas of interest include not only fundamental biological systems and drug discovery, but also applications to health, medical practice and implementation, big data, biotechnology, food science, human behaviour, broader biological systems and industrial applications of systems biology.
We encourage all approaches, including network biology, application of control theory to biological systems, computational modelling and analysis, comprehensive and/or high-content measurements, theoretical, analytical and computational studies of system-level properties of biological systems and computational/software/data platforms enabling such studies.