The Subcellular Distribution of an RNA Quality Control Protein, the Ro Autoantigen, is Regulated by Noncoding Y RNA Binding

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2009 Jan 1

PMID 19116308

Citations 47

Authors

Soyeong Sim

David E Weinberg

Gabriele Fuchs

Keum Choi

Jina Chung

Sandra L Wolin

Affiliations

Soon will be listed here.

Abstract

The Ro autoantigen is a ring-shaped RNA-binding protein that binds misfolded RNAs in nuclei and is proposed to function in quality control. In the cytoplasm, Ro binds noncoding RNAs, called Y RNAs, that inhibit access of Ro to other RNAs. Ro also assists survival of mammalian cells and at least one bacterium after UV irradiation. In mammals, Ro undergoes dramatic localization changes after UV irradiation, changing from mostly cytoplasmic to predominantly nuclear. Here, we report that a second role of Y RNAs is to regulate the subcellular distribution of Ro. A mutant Ro protein that does not bind Y RNAs accumulates in nuclei. Ro also localizes to nuclei when Y RNAs are depleted. By assaying chimeric proteins in which portions of mouse Ro were replaced with bacterial Ro sequences, we show that nuclear accumulation of Ro after irradiation requires sequences that overlap the Y RNA binding site. Ro also accumulates in nuclei after oxidative stress, and similar sequences are required. Together, these data reveal that Ro contains a signal for nuclear accumulation that is masked by a bound Y RNA and suggest that Y RNA binding may be modulated during cell stress.

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References

Chen X, Smith J, Shi H, Yang D, Flavell R, Wolin S . The Ro autoantigen binds misfolded U2 small nuclear RNAs and assists mammalian cell survival after UV irradiation. Curr Biol. 2003; 13(24):2206-11. DOI: 10.1016/j.cub.2003.11.028. View

Matsuoka S, Ballif B, Smogorzewska A, McDonald 3rd E, Hurov K, Luo J . ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007; 316(5828):1160-6. DOI: 10.1126/science.1140321. View

Liang X, Liu Q, Michaeli S . Small nucleolar RNA interference induced by antisense or double-stranded RNA in trypanosomatids. Proc Natl Acad Sci U S A. 2003; 100(13):7521-6. PMC: 164619. DOI: 10.1073/pnas.1332001100. View

Neher S, Bradshaw N, Floor S, Gross J, Walter P . SRP RNA controls a conformational switch regulating the SRP-SRP receptor interaction. Nat Struct Mol Biol. 2009; 15(9):916-23. PMC: 2767265. DOI: 10.1038/nsmb.1467. View

Elbashir S, Martinez J, Patkaniowska A, Lendeckel W, Tuschl T . Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J. 2001; 20(23):6877-88. PMC: 125328. DOI: 10.1093/emboj/20.23.6877. View

Mariner P, Walters R, Espinoza C, Drullinger L, Wagner S, Kugel J . Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol Cell. 2008; 29(4):499-509. DOI: 10.1016/j.molcel.2007.12.013. View

Tarn W, Yario T, Steitz J . U12 snRNA in vertebrates: evolutionary conservation of 5' sequences implicated in splicing of pre-mRNAs containing a minor class of introns. RNA. 1995; 1(6):644-56. PMC: 1369308. View

Matera A, Frey M, Margelot K, Wolin S . A perinucleolar compartment contains several RNA polymerase III transcripts as well as the polypyrimidine tract-binding protein, hnRNP I. J Cell Biol. 1995; 129(5):1181-93. PMC: 2120477. DOI: 10.1083/jcb.129.5.1181. View

Gwizdek C, Ossareh-Nazari B, Brownawell A, Doglio A, Bertrand E, Macara I . Exportin-5 mediates nuclear export of minihelix-containing RNAs. J Biol Chem. 2003; 278(8):5505-8. DOI: 10.1074/jbc.C200668200. View

10.

Wang D, Buyon J, Chan E . Cloning and expression of mouse 60 kDa ribonucleoprotein SS-A/Ro. Mol Biol Rep. 1996; 23(3-4):205-10. DOI: 10.1007/BF00351170. View

11.

GREEN C, Long K, Shi H, Wolin S . Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix. RNA. 1998; 4(7):750-65. PMC: 1369656. DOI: 10.1017/s1355838298971667. View

12.

BOUFFARD P, Barbar E, Briere F, Boire G . Interaction cloning and characterization of RoBPI, a novel protein binding to human Ro ribonucleoproteins. RNA. 2000; 6(1):66-78. PMC: 1369894. DOI: 10.1017/s1355838200990277. View

13.

Stein A, Fuchs G, Fu C, Wolin S, Reinisch K . Structural insights into RNA quality control: the Ro autoantigen binds misfolded RNAs via its central cavity. Cell. 2005; 121(4):529-539. PMC: 1769319. DOI: 10.1016/j.cell.2005.03.009. View

14.

Ramesh A, Savva C, Holzenburg A, Sacchettini J . Crystal structure of Rsr, an ortholog of the antigenic Ro protein, links conformational flexibility to RNA binding activity. J Biol Chem. 2007; 282(20):14960-7. DOI: 10.1074/jbc.M611163200. View

15.

Rutjes S, Lund E, van der Heijden A, Grimm C, van Venrooij W, Pruijn G . Identification of a novel cis-acting RNA element involved in nuclear export of hY RNAs. RNA. 2001; 7(5):741-52. PMC: 1370126. DOI: 10.1017/s1355838201002503. View

16.

Stokes M, Rush J, MacNeill J, Min Ren J, Sprott K, Nardone J . Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci U S A. 2007; 104(50):19855-60. PMC: 2148387. DOI: 10.1073/pnas.0707579104. View

17.

Todaro G, Green H . Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963; 17:299-313. PMC: 2106200. DOI: 10.1083/jcb.17.2.299. View

18.

Wassarman K . 6S RNA: a regulator of transcription. Mol Microbiol. 2007; 65(6):1425-31. DOI: 10.1111/j.1365-2958.2007.05894.x. View

19.

Hogg J, Collins K . Human Y5 RNA specializes a Ro ribonucleoprotein for 5S ribosomal RNA quality control. Genes Dev. 2007; 21(23):3067-72. PMC: 2081973. DOI: 10.1101/gad.1603907. View

20.

Kenan D, Query C, Keene J . RNA recognition: towards identifying determinants of specificity. Trends Biochem Sci. 1991; 16(6):214-20. DOI: 10.1016/0968-0004(91)90088-d. View