Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network

JOURNAL OF THEORETICAL BIOLOGY

卷:481

Article

Dhawan, Andrew¹  Harris, Adrian L.¹  Buffa, Francesca M.¹  Scott, Jacob G.^2,3 

[1] Univ Oxford, Dept Oncol, Oxford, England

[2] Cleveland Clin, Dept Translat Hematol, Cleveland, OH 44106 USA

[3] Cleveland Clin, Dept Oncol Res, Cleveland, OH 44106 USA

关键词: miRNA;    miRNA sponge;    circRNA;    non-coding RNA;    RNA network;   

DOI  :  10.1016/j.jtbi.2018.10.055

来源: Elsevier

【 摘 要 】

Oscillations are crucial to the normal function of living organisms, across a wide variety of biological processes. In eukaryotes, oscillatory dynamics are thought to arise from interactions at the protein and RNA levels; however, the role of non-coding RNA in regulating these dynamics remains understudied. In this work, we show how non-coding RNA acting as microRNA (miRNA) sponges in a conserved miRNA transcription factor feedback motif, can give rise to oscillatory behaviour, and how to test for this experimentally. Control of these non-coding RNA can dynamically create oscillations or stability, and we show how this behaviour predisposes to oscillations in the stochastic limit. These results, supported by emerging evidence for the role of miRNA sponges in development, point towards key roles of different species of miRNA sponges, such as circular RNA, potentially in the maintenance of yet unexplained oscillatory behaviour. These results help to provide a paradigm for understanding functional differences between the many redundant, but distinct RNA species thought to act as miRNA sponges in nature, such as long non-coding RNA, pseudogenes, competing mRNA, circular RNA, and3' UTRs. (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

Free