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Noise control is a primary function of microRNAs and post-transcriptional regulation

View ORCID ProfileJörn M. Schmiedel, View ORCID ProfileDebora S. Marks, View ORCID ProfileBen Lehner, View ORCID ProfileNils Blüthgen
doi: https://doi.org/10.1101/168641
Jörn M. Schmiedel
1Institute of Pathology, Charité – Universitätsmedizin Berlin, 10117 Berlin, Germany
4Universitat Pompeu Fabra, 08003 Barcelona, Spain
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Debora S. Marks
5Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
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Ben Lehner
3EMBL-CRG Systems Biology Unit, Centre for Genomic Regulation (CRG), European Molecular Biology Organization, 08003 Barcelona, Spain
4Universitat Pompeu Fabra, 08003 Barcelona, Spain
6Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain
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Nils Blüthgen
1Institute of Pathology, Charité – Universitätsmedizin Berlin, 10117 Berlin, Germany
2IRI Life Sciences, Humboldt Universität Berlin, 10115 Berlin, Germany
7Berlin Institute of Health, 10178 Berlin, Germany
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  • For correspondence: nils.bluethgen@charite.de
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Abstract

microRNAs are pervasive post-transcriptional regulators of protein-coding genes in multicellular organisms. Two fundamentally different models have been proposed for the function of microRNAs in gene regulation. In the first model, microRNAs act as repressors, reducing protein concentrations by accelerating mRNA decay and inhibiting translation. In the second model, in contrast, the role of microRNAs is not to reduce protein concentrations per se but to reduce fluctuations in these concentrations. Here we present genome-wide evidence that mammalian microRNAs frequently function as noise controllers rather than repressors. Moreover, we show that post-transcriptional noise control has been widely adopted across species from bacteria to animals, with microRNAs specifically employed to reduce noise in regulatory and context-specific processes in animals. Our results substantiate the detrimental nature of expression noise, reveal a universal strategy to control it, and suggest that microRNAs represent an evolutionary innovation for adaptive noise control in animals.

Highlights

  • Genome-wide evidence that microRNAs function as noise controllers for genes with context-specific functions

  • Post-transcriptional noise control is universal from bacteria to animals

  • Animals have evolved noise control for regulatory and context-specific processes

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 26, 2017.
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Noise control is a primary function of microRNAs and post-transcriptional regulation
Jörn M. Schmiedel, Debora S. Marks, Ben Lehner, Nils Blüthgen
bioRxiv 168641; doi: https://doi.org/10.1101/168641
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Noise control is a primary function of microRNAs and post-transcriptional regulation
Jörn M. Schmiedel, Debora S. Marks, Ben Lehner, Nils Blüthgen
bioRxiv 168641; doi: https://doi.org/10.1101/168641

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