Abstract
Werner syndrome (WS) is a rare autosmomal recessive genetic disorder causing premature aging. The gene (WRN) responsible for WS encodes a protein homologous to the RecQ-type helicase. WRN has a nucleolar localization signal and shows intranuclear trafficking between the nucleolus and the nucleoplasm. WRN is recruited into the nucleolus when rRNA transcription is reactivated in quiescent cells. Inhibition of mRNA transcription with α-amanitin has no effect on nucleolar localization of WRN whereas inhibition of rRNA transcription with actinomycin D releases WRN from nucleoli, suggesting that nucleolar WRN is closely related to rRNA transcription by RNA polymerase I (RPI). A possible function of WRN on rRNA transcription through interaction with RPI is supported by the results described here showing that WRN is co-immunoprecipitated with an RPI subunit, RPA40. Here we show that WS fibroblasts are characterized by a decreased level of rRNA transcription compared with wild-type cells, and that the decreased level of rRNA transcription in WS fibroblasts recovers when wild-type WRN is exogenously expressed. By contrast, exogenously expressed mutant-type WRN lacking an ability to migrate into the nucleolus fails to stimulate rRNA transcription. These results suggest that WRN promotes rRNA transcription as a component of an RPI-associated complex in the nucleolus.
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Acknowledgements
The authors would like to thank Lawrence I Rothblum at Sigfried and Janet Weis Center for Research, the Geisinger Clinic in USA for his generous gift of anti-A127, anti-A194 and anti-RAP74 antibodies. We would like to acknowledge Martin Lavin at Queensland Institute of Medical Research in Australia for critically reading the manuscript. This study was supported by the Drug Organization (The Organization for Drug ADR Relief, R and D Promotion and Product Review) of the Japanese Government.
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Shiratori, M., Suzuki, T., Itoh, C. et al. WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex. Oncogene 21, 2447–2454 (2002). https://doi.org/10.1038/sj.onc.1205334
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DOI: https://doi.org/10.1038/sj.onc.1205334
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