X. Chen, H. Shi, J. Smith, D. Yang,¹ L. Evangelisti,¹ R. Flavell¹ and Sandra Wolin, M.D., Ph.D.

Department of Cell Biology

Yale University

The Ro 60 kDa autoantigen is an RNA-binding protein that is normally bound to small cytoplasmic RNAs known as Y RNAs. Although these RNPs are components of most vertebrate cells, their function has long been mysterious. In Xenopus oocyte nuclei, the Ro protein is also complexed with a large class of variant 5S rRNA precursors. Because these variant RNAs are inefficiently processed to mature 5S rRNA and eventually degraded, the Ro protein may recognize improperly folded 5S rRNA precursors as part of a quality control pathway (O’Brien and Wolin, Genes & Dev. 8:2891-2903).

Although Ro RNPs have not been detected in either S. cerevisiae or S. pombe, the genome of the radiation-resistant eubacterium Deinococcus radiodurans contains an orthologue of the Ro protein. The Ro protein orthologue, Rsr (Ro Sixty Related) contributes to the resistance of D. radiodurans to ultraviolet irradiation. D. radiodurans cells lacking rsr are more sensitive to UV irradiation than wild-type cells. During recovery from irradiation, the levels of Rsr increase approximately fourfold. Rsr binds several small RNAs, encoded upstream of rsr, that also accumulate during recovery from UV irradiation. Remarkably, one of these RNAs resembles the Y RNAs bound by the Ro autoantigen in higher eukaryotes (Chen et al., Genes & Dev. 14:777-82).

We have been examining the role of Ro RNPs in the recovery of higher cells following UV irradiation. Using gene knockout technology, we generated mouse embryonic stem cells that lack the Ro protein. Mouse cells lacking Ro have drastically reduced levels of Y RNAs, suggesting that Ro protein binding stabilizes these RNAs from degradation. Most interestingly, cells lacking the Ro protein are more sensitive to ultraviolet light than wild-type cells. Thus, in both mouse and bacterial cells, Ro RNPs contribute to survival following radiation damage. Although the mechanism is under investigation, one possibility is that the Ro protein binds to misfolded, mutant RNAs that are transcribed from DNA molecules containing radiation-induced mutations.

Front Matter (R1-R10)

Selected Invited Conference Papers1 Markey Scholars Update (1-6)

2 Ensuring the Future Participation of Women in Science, Mathematics, and Engineering (7-12)

3 The Future of Non-profit Funding in Biomedical Research (13-23)

4 New Directions in Genomic Research (24-28)

Papers Presented by Markey Scholars5 Functional Genomics (29-41)

6 Electrophysiology of Synapses (42-49)

7 Transcription, Chromatin Assembly, and Homologous Recombination in Chromatin (50-72)

8 The New Biology (73-79)

9 Signal Transduction in Bacteria (80-89)

10 AAK1, A Novel Kinase That Regulates Cargo Selection for Clatherin-Mediated Endocytosis (90-96)

11 Abstracts of Poster Sessions (97-152)

Appendix A: Conference Agenda (153-157)

Appendix B: Speakers Biographical Sketches (158-161)

Appendix C: Conference Participants (162-166)