Differential association of microRNAs with polysomes reflects distinct strengths of interactions with their mRNA targets
Open accessAbstract
While microRNAs have been shown to copurify with polysomes, their relative fraction in the translation pool (polysome occupancy) has not yet been measured. Here, we introduce a high-throughput method for quantifying polysome occupancies of hundreds of microRNAs and use it to investigate factors affecting these occupancies. Analysis in human embryonic stem cells (hESCs) and foreskin fibroblasts (hFFs) revealed microRNA-specific preferences for low, medium, or high polysome occupancy. Bioinformatics and functional analysis based on overexpression of endogenous and chimeric microRNAs showed that the polysome occupancy of microRNAs is specified by its mature sequence and depends on the choice of seed. Nuclease treatment further suggested that the differential occupancy of the microRNAs reflects interactions with their mRNA targets. Indeed, analysis of microNRA•mRNA duplexes showed that pairs involving high occupancy microRNAs exhibit significantly higher binding energy compared to pairs with low occupancy microRNAs. Since mRNAs reside primarily in polysomes, strong interactions lead to high association of microRNAs with polysomes and vice versa for weak interactions. Comparison between hESCs and hFFs data revealed that hESCs tend to express lower occupancy microRNAs, suggesting that cell type-dependent translational features may be affected by expression of a particular set of microRNAs.
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mRNAs with higher affinity MREs generally show greater sensitivity to miRNA-mediated post-transcriptional repression.
“On the other hand, mRNAs with higher affinity MREs generally show greater sensitivity to miRNA-mediated post-transcriptional repression (84, 94).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [84]
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- Authors
- Molotski, N., & Soen, Y.
- Affiliations
- Weizmann Institute of Science (IL)
- ORCID
- Soen, Yoav
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-07-26
- Volume
- 18
- Issue
- 9
- Pages
- 1612-1623
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC3425777
- OpenAlex
- W2124089217
- Cited by
- 26
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2018: 6 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Weizmann Institute of Science
- Israel Science Foundation
- Wolfson Family Charitable Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- microRNA, miRNA-mRNA interactions, seed sequence, translation (biology), human embryonic stem cells, foreskin fibroblasts, cell type-specific translation, microRNA overexpression
- MeSH terms
- Cell Line, Humans, Polyribosomes, Protein Binding, RNA, Messenger, Gene Expression, MicroRNAs, Embryonic Stem Cells
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