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Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation
Abstract
Most of what is presently known about how miRNAs regulate gene expression comes from studies that characterized the regulatory effect of miRNA binding sites located in the 3′ untranslated regions (UTR) of mRNAs. In recent years, there has been increasing evidence that miRNAs also bind in the coding region (CDS), but the implication of these interactions remains obscure because they have a smaller impact on mRNA stability compared with miRNA-target interactions that involve 3′ UTRs. Here we show that miRNA-complementary sites that are located in both CDS and 3′-UTRs are under selection pressure and share the same sequence and structure properties. Analyzing recently published data of ribosome-protected fragment profiles upon miRNA transfection from the perspective of the location of miRNA-complementary sites, we find that sites located in the CDS are most potent in inhibiting translation, while sites located in the 3′ UTR are more efficient at triggering mRNA degradation. Our study suggests that miRNAs may combine targeting of CDS and 3′ UTR to flexibly tune the time scale and magnitude of their post-transcriptional regulatory effects.
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“This difference in potency is consistent with prior studies, and more recent data support that miRNA binding to CDS primarily inhibits translation (Hausser et al., 2013).”
From Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain (2014) · cites this paper as Hausser et al., 2013
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“For comparison, we estimated the average phastCons conservation score (Siepel et al. 2005) for CDS and 39 UTR occurrences of individual motifs, and found a similar but weaker correlation (Supplemental Fig.”
ResultThe impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592
Widespread changes in protein synthesis induced by microRNAs
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BackgroundMethodResultInfluentialWidespread translational inhibition by plant miRNAs and siRNAs
Brodersen, P., Sakvarelidze-Achard, L., Bruun-Rasmussen, M., Dunoyer, P., Yamamoto, Y. Y., Sieburth, L., & Voinnet, O. (2008) · Science · doi:10.1126/science.1159151 · Cited by 1,477
Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish
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“In the Bazzini et al. (2012) data, however, what is observed is preferential stabilization of known dre-miR-430 targets, which suggests either a direct involvement of miRNA-dependent regulation or an indirect correlation caused by the overlap between the set of mRNAs that undergo polyadenylation…”
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Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain
Boudreau, R. L., Jiang, P., Gilmore, B. L., Spengler, R. M., Tirabassi, R., Nelson, J. A., Ross, C. A., Xing, Y., & Davidson, B. L. (2014) · Neuron · doi:10.1016/j.neuron.2013.10.062 · Cited by 217
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Metadata
- Authors
- Hausser, J., Syed, A. P., Bilen, B., & Zavolan, M.
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-01-18
- Volume
- 23
- Issue
- 4
- Pages
- 604-615
- ISSN
- 1088-9051
- PMC
- PMC3613578
- Cited by
- 317
- References
- 8
- Language
- en
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