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Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity.

ABSTRACT: The Ro 60 kDa autoantigen is a major target of the immune response in patients with systemic lupus erythematosus. In vertebrate cells, Ro binds misfolded small RNAs and likely functions in RNA quality control. In eukaryotes and bacteria, Ro also associates with small RNAs called Y RNAs. We present structures of unliganded Ro and Ro complexed with two RNAs at 1.95 and 2.2 A resolution, respectively. Ro consists of a von Willebrand factor A domain and a doughnut-shaped domain composed of HEAT repeats. In the complex, a fragment of Y RNA binds on the outer surface of the HEAT-repeat ring, and single-stranded RNA binds in the toroid hole. Mutagenesis supports a binding site for misfolded RNAs that encompasses both sites, with a single-stranded end inserted into the toroid cavity. Our experiments suggest that one role of Y RNAs may be to regulate access of other RNAs to Ro.

SUBMITTER: Stein AJ

PROVIDER: S-EPMC1769319 | biostudies-literature | 2005 May

REPOSITORIES: biostudies-literature

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Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity.

Stein Adam J AJ Fuchs Gabriele G Fu Chunmei C Wolin Sandra L SL Reinisch Karin M KM

Cell 20050501 4

The Ro 60 kDa autoantigen is a major target of the immune response in patients with systemic lupus erythematosus. In vertebrate cells, Ro binds misfolded small RNAs and likely functions in RNA quality control. In eukaryotes and bacteria, Ro also associates with small RNAs called Y RNAs. We present structures of unliganded Ro and Ro complexed with two RNAs at 1.95 and 2.2 A resolution, respectively. Ro consists of a von Willebrand factor A domain and a doughnut-shaped domain composed of HEAT repe ...[more]

PMID: 15907467

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