title: The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV irradiation.
abstract: The Ro 60 kDa autoantigen, an RNA binding protein, is a major target of the immune response in patients with systemic lupus erythematosus. As mice lacking Ro develop a lupus-like syndrome, Ro may be important for preventing autoimmunity. However, the cellular function of Ro, which binds small cytoplasmic RNAs of unknown function called Y RNAs, has been enigmatic. Ro has been proposed to function in 5S rRNA quality control based on experiments in Xenopus laevis oocytes, and a Ro ortholog enhances survival of the eubacterium Deinococcus radiodurans after ultraviolet irradiation. To test the general importance of these two observations for Ro function, we investigated the role of Ro in mammalian cells. We report that, in mouse embryonic stem (ES) cells, Ro binds variant spliceosomal U2 snRNAs. Expression of mouse U2 snRNAs in Xenopus oocytes reveals that binding occurs in nuclei and appears to involve recognition of misfolded RNA. Moreover, mouse ES cells lacking Ro exhibit decreased survival after ultraviolet irradiation. In irradiated cells, both Ro and a Y RNA accumulate in nuclei. We propose that Ro plays a general role in small RNA quality control and that this function is important for cell survival after ultraviolet irradiation.
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Chen
authors.forename: James D
authors.initials: JD
authors.lastname: Smith
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Derek D
authors.initials: DD
authors.lastname: Yang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Wolin
mesh_terms: D000818:Animals; D001324:Autoantigens; D001483:Base Sequence; D015152:Blotting, Northern; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology; D011233:Precipitin Tests; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear / Q000235:genetics* / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D013234:Stem Cells; D014466:Ultraviolet Rays; D014981:Xenopus; D000099207:SS-A Antigen
chemical_list: D001324:Autoantigens; D020733:RNA, Small Cytoplasmic; D012342:RNA, Small Nuclear; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human; C405484:U2 small nuclear RNA