Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity.
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.
Stein
Adam J
AJ
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Fuchs
Gabriele
G
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Fu
Chunmei
C
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.
Wolin
Sandra L
SL
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
Reinisch
Karin M
KM
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510. Electronic address: karin.reinisch@yale.edu.
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D007313:Insecta; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D020733:RNA, Small Cytoplasmic / Q000737:chemistry / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D000099207:SS-A Antigen
D012313:RNA; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000099207:SS-A Antigen