Tan D, Zhou M, Kiledjian M, Tong L

A conserved stem-loop motif of the constitutive decay element (CDE) in the 3' UTR of mRNAs is recognized by the ROQ domain of Roquin, which mediates mRNA degradation. Here we report two crystal structures of the Homo sapiens ROQ domain in complex with CDE RNA. The ROQ domain has an elongated shape with three subdomains. The 19-nt Hmgxb3 CDE is bound as a stem-loop to domain III. The 23-nt TNF RNA is bound as a duplex to a separate site at the interface between domains I and II. Mutagenesis studies confirm that the ROQ domain has two separate RNA-binding sites, one for stem-loop RNA (A site) and the other for double-stranded RNA (B site). Mutation in either site perturbs the Roquin-mediated degradation of HMGXB3 and IL6 mRNAs in human cells, demonstrating the importance of both sites for mRNA decay.

Mesh Terms:
Amino Acid Substitution, Base Pairing, Base Sequence, Binding Sites, Crystallography, X-Ray, HEK293 Cells, HMGB Proteins, Humans, Hydrogen Bonding, Interleukin-6, Models, Molecular, Mutagenesis, Site-Directed, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, RNA Interference, RNA Stability, RNA, Messenger, RNA-Binding Proteins, Tumor Necrosis Factor-alpha, Ubiquitin-Protein Ligases

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