Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA

Lorenzo Baronti, Ileana Guzzetti, Parisa Ebrahimi, Sarah Friebe Sandoz, Emilie Steiner, Judith Schlagnitweit, Bastian Fromm, Luis Silva, Carolina Fontana, Alan A. Chen and Katja Petzold ()
Additional contact information
Lorenzo Baronti: Karolinska Institute
Ileana Guzzetti: Karolinska Institute
Parisa Ebrahimi: University at Albany, State University of New York
Sarah Friebe Sandoz: Karolinska Institute
Emilie Steiner: Karolinska Institute
Judith Schlagnitweit: Karolinska Institute
Bastian Fromm: The Wenner-Gren Institute, Stockholm University
Luis Silva: Karolinska Institute
Carolina Fontana: Karolinska Institute
Alan A. Chen: University at Albany, State University of New York
Katja Petzold: Karolinska Institute

Nature, 2020, vol. 583, issue 7814, 139-144

Abstract: Abstract MicroRNAs (miRNAs) regulate the levels of translation of messenger RNAs (mRNAs). At present, the major parameter that can explain the selection of the target mRNA and the efficiency of translation repression is the base pairing between the ‘seed’ region of the miRNA and its counterpart mRNA1. Here we use R1ρ relaxation-dispersion nuclear magnetic resonance2 and molecular simulations3 to reveal a dynamic switch—based on the rearrangement of a single base pair in the miRNA–mRNA duplex—that elongates a weak five-base-pair seed to a complete seven-base-pair seed. This switch also causes coaxial stacking of the seed and supplementary helix fitting into human Argonaute 2 protein (Ago2), reminiscent of an active state in prokaryotic Ago4,5. Stabilizing this transient state leads to enhanced repression of the target mRNA in cells, revealing the importance of this miRNA–mRNA structure. Our observations tie together previous findings regarding the stepwise miRNA targeting process from an initial ‘screening’ state to an ‘active’ state, and unveil the role of the RNA duplex beyond the seed in Ago2.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2336-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:583:y:2020:i:7814:d:10.1038_s41586-020-2336-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2336-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().