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

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.jtbi.2018.10.055

Authors


More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
Role:
Author
ORCID:
0000-0002-5027-1277
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Sub department:
CRUK/MRC Ox Inst for Radiation Oncology
Role:
Author
ORCID:
0000-0003-0409-406X
More by this author
Role:
Author
ORCID:
0000-0003-2971-7673


More from this funder
Funding agency for:
Dhawan, A
Grant:
Cancer Centre
CBIG:23969


Publisher:
Elsevier
Journal:
Journal of Theoretical Biology More from this journal
Volume:
481
Pages:
54-60
Publication date:
2018-10-30
Acceptance date:
2018-10-29
DOI:
EISSN:
1095-8541
ISSN:
0022-5193
Pmid:
30385313


Language:
English
Keywords:
Pubs id:
pubs:940882
UUID:
uuid:f5244c3b-6aee-4d01-9281-52e7e39359cf
Local pid:
pubs:940882
Source identifiers:
940882
Deposit date:
2018-12-03

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