The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Target mRNA abundance dilutes microRNA and siRNA activity
Open accessAbstract
Post‐transcriptional regulation by microRNAs and siRNAs depends not only on characteristics of individual binding sites in target mRNA molecules, but also on system‐level properties such as overall molecular concentrations. We hypothesize that an intracellular pool of microRNAs/siRNAs faced with a larger number of available predicted target transcripts will downregulate each individual target gene to a lesser extent. To test this hypothesis, we analyzed mRNA expression change from 178 microRNA and siRNA transfection experiments in two cell lines. We find that downregulation of particular genes mediated by microRNAs and siRNAs indeed varies with the total concentration of available target transcripts. We conclude that to interpret and design experiments involving gene regulation by small RNAs, global properties, such as target mRNA abundance, need to be considered in addition to local determinants. We propose that analysis of microRNA/siRNA targeting would benefit from a more quantitative definition, rather than simple categorization of genes as ‘target’ or ‘not a target.’ Our results are important for understanding microRNA regulation and may also have implications for siRNA design and small RNA therapeutics.
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Cites
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“…( n ¼ 4) of the transfection experiments whose small RNA had low target abundance ( n ¼ 12) resulted in predicted targets being highly downregulated, whereas there was only one exception experiment whose small RNA had high downregulation when there was high abundance of predicted targets ( n ¼ 20).”
InfluentialA microRNA component of the p53 tumour suppressor network
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Cited by
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
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Endogenous microRNA sponges: evidence and controversy
Thomson, D. W., & Dinger, M. E. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.20 · Cited by 2,185
The biochemical basis of microRNA targeting efficacy
(2019) · doi:10.1126/science.aav1741 · Cited by 1,570
Roles for MicroRNAs in Conferring Robustness to Biological Processes
Ebert, M. S., & Sharp, P. A. (2012) · Cell · doi:10.1016/j.cell.2012.04.005 · Cited by 1,564
Metadata
- Authors
- Arvey, A., Larsson, E., Sander, C., Leslie, C. S., & Marks, D. S.
- Venue
- Molecular Systems Biology
- Published
- 2010-01
- Volume
- 6
- Issue
- 1
- Pages
- 363-363
- ISSN
- 1744-4292 (ISSN-L)
- OpenAlex
- W2098044274
- Cited by
- 335
- References
- 8
- FWCI
- 9.12
- Type
- journal article
- Language
- en
- Open access
- gold
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- Arvey, A., Larsson, E., Sander, C., Leslie, C. S., & Marks, D. S. (2010). Target mRNA abundance dilutes microRNA and siRNA activity. Molecular Systems Biology. https://doi.org/10.1038/msb.2010.24
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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