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Nucleic Acids Research Advance Access originally published online on February 22, 2008
Nucleic Acids Research 2008 36(7):2330-2337; doi:10.1093/nar/gkn088
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Nucleic Acids Research, 2008, Vol. 36, No. 7 2330-2337
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

RNA

Solution structure of a let-7 miRNA:lin-41 mRNA complex from C. elegans

Mirko Cevec, Christophe Thibaudeau and Janez Plavec*

Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia

*To whom correspondence should be addressed. Tel: +386 1 47 60 353; Fax: +386 1 47 60 300; Email: janez.plavec{at}ki.si

Received December 24, 2007. Revised February 6, 2008. Accepted February 11, 2008.

let-7 microRNA (miRNA) regulates heterochronic genes in developmental timing of the nematode Caenorhabditis elegans. Binding of miRNA to messenger RNA (mRNA) and structural features of the complex are crucial for gene silencing. We herein present the NMR solution structure of a model mimicking the interaction of let-7 miRNA with its complementary site (LCS 2) in the 3' untranslated region (3'-UTR) of the lin-41 mRNA. A structural study was performed by NMR spectroscopy using NOE restraints, torsion angle restraints and residual dipolar couplings. The 33-nt RNA construct folds into a stem–loop structure that features two stem regions which are separated by an asymmetric internal loop. One of the stems comprises a GU wobble base pair, which does not alter its overall A-form RNA conformation. The asymmetric internal loop adopts a single, well-defined structure in which three uracils form a base triple, while two adenines form a base pair. The 3D structure of the construct gives insight into the structural aspects of interactions between let-7 miRNA and lin-41 mRNA.


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