MicroRNA control of protein expression noise
Open accessAbstract
MicroRNAs (miRNAs) repress the expression of many genes in metazoans by accelerating messenger RNA degradation and inhibiting translation, thereby reducing the level of protein. However, miRNAs only slightly reduce the mean expression of most targeted proteins, leading to speculation about their role in the variability, or noise, of protein expression. We used mathematical modeling and single-cell reporter assays to show that miRNAs, in conjunction with increased transcription, decrease protein expression noise for lowly expressed genes but increase noise for highly expressed genes. Genes that are regulated by multiple miRNAs show more-pronounced noise reduction. We estimate that hundreds of (lowly expressed) genes in mouse embryonic stem cells have reduced noise due to substantial miRNA regulation. Our findings suggest that miRNAs confer precision to protein expression and thus offer plausible explanations for the commonly observed combinatorial targeting of endogenous genes by multiple miRNAs, as well as the preferential targeting of lowly expressed genes.
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miRNAs may play key roles in the post-transcriptional reduction of expression noise.
“Intriguingly, miRNA do not solely, or maybe even predominantly, function as target-specific regulators but may play key roles in the post-transcriptional reduction of expression noise (89, 90).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [90]
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- Authors
- Schmiedel, J. M., Klemm, S. L., Zheng, Y., Sahay, A., Blüthgen, N., Marks, D. S., & van Oudenaarden, A.
- Affiliations
- Humboldt-Universität zu Berlin (DE)
- Massachusetts Institute of Technology (US)
- Harvard University (US)
- Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge MA 02139, USA.
- Corresponding author
- Blüthgen, Nils
- Marks, Debora S.
- Venue
- Science
- Published
- 2015-04-03
- Volume
- 348
- Issue
- 6230
- Pages
- 128-132
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2020596227
- Cited by
- 395
- References
- 29
- Citations by year
- 2026: 24 · 2025: 24 · 2024: 24 · 2023: 25 · 2022: 29 · 2021: 27 · 2020: 33 · 2019: 50 · 2018: 48 · 2017: 47 · 2016: 36 · 2015: 28
- FWCI
- 17.64
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- European Molecular Biology Organization
- Harvard Medical School
- European Research Council (ERC-AdG 294325-GeneNoiseControl)
- Deutsche Forschungsgemeinschaft (GK1772, SPP1395)
- Bundesministerium für Bildung und Forschung
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Koch Institute for Integrative Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- microRNA, protein expression noise, gene expression variation, mRNA degradation, protein synthesis inhibition, transcription, lowly expressed genes, mouse embryonic stem cells, mathematical modeling
- MeSH terms
- Animals, Gene Expression Regulation, Models, Genetic, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, 3' Untranslated Regions, MicroRNAs, Mice, Embryonic Stem Cells, Single-Cell Analysis
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