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Vol. 20, Issue 5, 1555-1564, March 1, 2009

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

Soyeong Sim^*, David E. Weinberg^,, Gabriele Fuchs^*,, Keum Choi^*,||, Jina Chung^*, and Sandra L. Wolin^*,

Departments of *Cell Biology and Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536

Submitted November 4, 2008; Revised December 11, 2008; Accepted December 19, 2008
Monitoring Editor: A. Gregory Matera

InCytes from MBC

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.

Present addresses: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305;

^|| Korean Food and Drug Administration, Seoul, Korea.

Address correspondence to: Sandra L. Wolin (sandra.wolin{at}yale.edu)

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