Structural basis for recognition of AU-rich element RNA by the HuD protein.
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 A), and with an 11-nucleotide fragment of a class II ARE (the tumor necrosis factor alpha ARE; to 2.3 A). 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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Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Tanaka Hall
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D020856:AT Rich Sequence / Q000235:genetics*; D000595:Amino Acid Sequence; D001665:Binding Sites; D016384:Consensus Sequence / Q000235:genetics; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D016415:Sequence Alignment; D013379:Substrate Specificity; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D029721:Drosophila Proteins; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C067777:Sxl protein, Drosophila; D014409:Tumor Necrosis Factor-alpha