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Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d

Nature Structural & Molecular Biology volume 11, pages 257–264 (2004)Cite this article

Abstract

The tandem zinc finger (TZF) domain of the protein TIS11d binds to the class II AU-rich element (ARE) in the 3′ untranslated region (3′ UTR) of target mRNAs and promotes their deadenylation and degradation. The NMR structure of the TIS11d TZF domain bound to the RNA sequence 5′-UUAUUUAUU-3′ comprises a pair of novel CCCH fingers of type CX8CX5CX3H separated by an 18-residue linker. The two TIS11d zinc fingers bind in a symmetrical fashion to adjacent 5′-UAUU-3′ subsites on the single-stranded RNA via a combination of electrostatic and hydrogen-bonding interactions, with intercalative stacking between conserved aromatic side chains and the RNA bases. Sequence specificity in RNA recognition is achieved by a network of intermolecular hydrogen bonds, mostly between TIS11d main-chain functional groups and the Watson-Crick edges of the bases. The TIS11d structure provides insights into the RNA-binding functions of this large family of CCCH zinc finger proteins.

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Figure 1: Sequence alignment of TIS11d proteins.
Figure 2: NMR spectra of TIS11d protein free and bound to RNA.
Figure 3: Solution structure of the RNA complex of TIS11d.
Figure 4: Molecular recognition of RNA by TIS11d and hydrogen bonding between TIS11d and RNA.

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Protein Data Bank

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Acknowledgements

We thank B. Lee, M. Hennig, J. Williamson and D. Case for invaluable discussions, J. Chung and G. Kroon for assistance with NMR experiments, and M. Allen and L. Tennant for technical assistance. This work was supported by a grant from the US National Institutes of Health and by the Skaggs Institute for Chemical Biology.

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  1. Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Brian P Hudson, Maria A Martinez-Yamout, H Jane Dyson & Peter E Wright

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Correspondence to Peter E Wright.

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Hudson, B., Martinez-Yamout, M., Dyson, H. et al. Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d. Nat Struct Mol Biol 11, 257–264 (2004). https://doi.org/10.1038/nsmb738

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