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MICRORNAS

From transient recognition to efficient silencing: a RISCky business

Nature Structural & Molecular Biology volume 27, pages 519–520 (2020)Cite this article

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Cellular protein levels are finely tuned through microRNA-mediated gene regulation, triggered by RNA-induced silencing complexes (RISCs) that recognize, bind and silence mRNA targets. A recent study shows that, while mRNA target recognition is achieved with only about a third of the guide RNA sequence, formation of an efficient RISC conformation required for target silencing involves the coordination of transient structural states of the entire guide RNA–mRNA duplex.

Mature microRNAs (miRNAs) are small non-coding single-stranded RNAs containing approximately 22 nucleotides. They function in post-transcriptional gene regulation by guiding RNA-induced silencing complexes (RISCs) to complementary mRNAs to trigger silencing of these targets. In Nature, Baronti, Guzzetti, Ebrahimi and coworkers provide evidence that RNA structural dynamics play a critical role in the coordination of interactions between RISCs and target mRNAs1. The authors used R1ρ relaxation dispersion nuclear magnetic resonance (NMR) and molecular simulation to visualize the structural dynamics of the interaction between miR-34a and its miRNA recognition element (MRE) in the 3′UTR of Sirt1 (silent information regulator 1). Sirt1 and miR-34a participate in a tumor-suppressive positive feedback loop involving p53: Sirt1 deacetylates and inactivates p53, while p53 promotes the expression of miR-34a2, which in turn negatively regulates Sirt1, thereby increasing p53 activity3.

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Fig. 1: Three states of RISC.

References

  1. Baronti, L. et al. Nature https://doi.org/10.1038/s41586-020-2336-3 (2020).

  2. He, L. et al. Nature 447, 1130–1134 (2007).

    Article  CAS  Google Scholar 

  3. Yamakuchi, M. & Lowenstein, C. J. Cell Cycle 8, 712–715 (2009).

    Article  CAS  Google Scholar 

  4. Hammond, S. M., Bernstein, E., Beach, D. & Hannon, G. J. Nature 404, 293–296 (2000).

    Article  CAS  Google Scholar 

  5. Bartel, D. P. Cell 136, 215–233 (2009).

    Article  CAS  Google Scholar 

  6. Schirle, N. T. & MacRae, I. J. Science 336, 1037–1040 (2012).

    Article  CAS  Google Scholar 

  7. Agarwal, V., Bell, G. W., Nam, J.-W. & Bartel, D. P. Elife 4, e05005 (2015).

    Article  Google Scholar 

  8. Grimson, A. et al. Mol. Cell 27, 91–105 (2007).

    Article  CAS  Google Scholar 

  9. Sheu-Gruttadauria, J., Xiao, Y., Gebert, L. F. R. & MacRae, I. J. EMBO J. 38, e101153 (2019).

    Article  Google Scholar 

  10. Wang, Y. et al. Nature 461, 754–761 (2009).

    Article  CAS  Google Scholar 

  11. Chi, S. W., Hannon, G. J. & Darnell, R. B. Nat. Struct. Mol. Biol. 19, 321–327 (2012).

    Article  CAS  Google Scholar 

  12. Song, J.-J., Smith, S. K., Hannon, G. J. & Joshua-Tor, L. Science 305, 1434–1437 (2004).

    Article  CAS  Google Scholar 

  13. Broughton, J. P., Lovci, M. T., Huang, J. L., Yeo, G. W. & Pasquinelli, A. E. Mol. Cell 64, 320–333 (2016).

    Article  CAS  Google Scholar 

  14. Leontis, N. B. & Westhof, E. RNA 7, 499–512 (2001).

    Article  CAS  Google Scholar 

  15. Becker, W. R. et al. Mol. Cell 75, 741–755.e11 (2019).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank M. Dupont and E. Gagnon for critical reading of this article.

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  1. Institute for Research in Immunology and Cancer and Department of Computer Science and Operations Research, Université de Montréal, Montreal, QC, Canada

    François Major

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  1. François Major
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Correspondence to François Major.

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Major, F. From transient recognition to efficient silencing: a RISCky business. Nat Struct Mol Biol 27, 519–520 (2020). https://doi.org/10.1038/s41594-020-0451-3

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  • DOI: https://doi.org/10.1038/s41594-020-0451-3

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