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Structural basis for recognition of AU-rich element RNA by the HuD protein

Nature Structural Biology volume 8, pages 141–145 (2001)Cite this article

Abstract

Hu proteins bind to adenosine-uridine (AU)-rich elements (AREs) in the 3′ untranslated regions of many short-lived mRNAs, thereby stabilizing them. Here we report the crystal structures of the first two RNA recognition motif (RRM) domains of the HuD protein in complex with an 11-nucleotide fragment of a class I ARE (the c-fos ARE; to 1.8 Å), and with an 11-nucleotide fragment of a class II ARE (the tumor necrosis factor α ARE; to 2.3 Å). These structures reveal a consensus RNA recognition sequence that suggests a preference for pyrimidine-rich sequences and a requirement for a central uracil residue in the clustered AUUUA repeats found in class II AREs. Comparison to structures of other RRM domain–nucleic acid complexes reveals two base recognition pockets in all the structures that interact with bases using residues in conserved ribonucleoprotein motifs and at the C-terminal ends of RRM domains. Different conformations of nucleic acid can be bound by RRM domains by using different combinations of base recognition pockets and multiple RRM domains.

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Figure 1: Structure of the HuD1,2–cfos-11 complex.
Figure 2: Protein–RNA contacts.
Figure 3: Comparison of the HuD1,2–cfos-11 and Sxl–tra complexes.
Figure 4: Nucleic acid recognition by RRM domains.

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Acknowledgements

We thank G. Spizz for generously providing the human fetal brain cDNA; S. Strachan for initial cloning of expression constructs; W. Lai for performing preliminary RNA binding experiments; T. Transue for suggestions on RNA oligonucleotide design; C. Matson for assistance with crystallization; L. Pedersen, Z. Dauter and the staff of X9-B for assistance with data collection; J. Krahn for computer support and advice on crystallography; and P. Blackshear, D. Leahy, and K. Weeks for critical comments on this manuscript.

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  1. Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, USA

    Xiaoqiang Wang & Traci M. Tanaka Hall

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  1. Xiaoqiang Wang
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Correspondence to Traci M. Tanaka Hall.

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Wang, X., Tanaka Hall, T. Structural basis for recognition of AU-rich element RNA by the HuD protein. Nat Struct Mol Biol 8, 141–145 (2001). https://doi.org/10.1038/84131

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