Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

WRN helicase accelerates the transcription of ribosomal RNA as a component of an RNA polymerase I-associated complex

Oncogene volume 21, pages 2447–2454 (2002)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Balajee AS, Machwe A, May A, Gray MD, Oshima J, Martin GM, Nehlin JO, Brosh R, Orren DK, Bohr VA . 1999 Mol. Biol. Cell 10: 2655–2668

  • Brosh Jr RM, Orren DK, Nehlin JO, Ravn PH, Kenny MK, Machwe A, Bohr VA . 1999 J. Biol. Chem. 274: 18341–18350

  • Cheng RZ, Murano S, Kurz B, Shmookler Reis RJ . 1990 Mutat Res. 237: 259–269

  • Constantinou A, Tarsounas M, Karow JK, Brosh RM, Bohr VA, Hickson ID, West SC . 2000 EMBO Reports 1: 80–84

  • Cooper MP, Machwe A, Orren DK, Brosh RM, Ramsden D, Bohr VA . 2000 Genes Dev. 14: 907–912

  • Dammann R, Pfeifer GP . 1998 Biochem. Biophys. Acta 1396: 153–157

  • Epstein CJ, Martin GM, Schultz AL, Motulsky AG . 1966 Medicine 45: 177–221

  • Faragher RG, Kill IR, Hunter JA, Pope FM, Tannock C, Shall S . 1993 Proc. Natl. Acad. Sci. USA 90: 12030–12034

  • Finkelstein A, Kostrub CF, Li J, Chavez DP, Wang BQ, Fang SM, Greenblatt J, Burton ZF . 1992 Nature 355: 464–467

  • Fukuchi K, Martin GM, Monnat Jr RJ . 1989 Proc. Natl. Acad. Sci. USA 86: 5893–5897

  • Gangloff S, McDonald JP, Bendixen C, Arthur L, Rothstein R . 1994 Mol. Cell. Biol. 14: 8391–8398

  • Gray MD, Wang L, Youssourfian H, Martin GM, Oshima J . 1998 Exp. Cell Res. 242: 487–494

  • Huang S, Li B, Gray MD, Oshima J, Mian IS, Campisi J . 1998 Nat. Genet. 20: 114–116

  • Kadener S, Cramer P, Nogues G, Cazalla D, de La Mata M, Fededa JP, Werbajh SE, Srebrow A, Kornblihtt AR . 2001 EMBO J. 20: 5759–5768

  • Kamath-Loeb AS, Johansson E, Burgers PM, Loeb LA . 2000 Proc. Natl. Acad. Sci. USA 97: 4603–4608

  • Kamath-Loeb AS, Shen JC, Loeb LA, Fry M . 1998 J. Biol. Chem. 273: 34145–34150

  • Kitao S, Lindor NM, Shiratori M, Furuichi Y, Shimamoto A . 1999 Genomics 61: 268–276

  • Lebel M, Leder P . 1998 Proc. Natl. Acad. Sci. USA 95: 13097–13102

  • Lebel M, Spillare EA, Harris CC, Leder P . 1999 J. Biol. Chem. 274: 37795–37799

  • Lee S-K, Johnson RE, Yu S-L, Prakash L, Prakash S . 1999 Science 286: 2339–2342

  • Lombard DB, Beard C, Johnson B, Marciniak RA, Dausman J, Bronson R, Buhlmann JE, Lipman R, Curry R, Sharpe A, Jaenisch R, Guarente L . 2000 Mol. Cell. Biol. 20: 3286–3291

  • Marciniak RA, Lombard DB, Johnson FB, Guarente L . 1998 Proc. Natl. Acad. Sci. USA 95: 6887–6892

  • Matsumoto T, Imamura O, Yamabe Y, Kuromitsu J, Tokutake Y, Shimamoto A, Suzuki N, Satoh M, Kitao S, Ichikawa K, Kataoka H, Sugaware K, Thomas W, Mason B, Tsuchihashi Z, Drayna D, Sugawara M, Sugimoto M, Furuichi Y, Goto M . 1997a Hum. Genet. 100: 123–130

  • Matsumoto T, Shimamoto A, Goto M, Furuichi Y . 1997b Nat. Genet. 16: 335–336

  • Miyake S, Makimura M, Kanegae Y, Harada S, Sato Y, Takamori K, Tokuda C, Saito I . 1996 Proc. Natl. Acad. Sci. USA 93: 1320–1324

  • Mushegian AR, Bassett Jr DE, Boguski MS, Bork P, Koonin EV . 1997 Proc. Natl. Acad. Sci. USA 94: 5831–5836

  • Niwa H, Yamamura K, Miyazaki J . 1991 Gene 108: 193–199

  • Rong L, Palladino F, Aguilera A, Klein HL . 1991 Genetics 127: 75–85

  • Rong L, Klein HL . 1993 J. Biol. Chem. 268: 1252–1259

  • Salk D, Au K, Hoehn H, Martin GM . 1981 Cytogenet. Cell. Genet. 30: 92–107

  • Salk D, Bryant E, Hoehn H, Johnston P, Martin GM . 1985 Adv. Exp. Med. Biol. 190: 305–311

  • Shen JC, Gray MD, Oshima J, Kamath-Loeb AS, Fry M, Loeb LA . 1998 J. Biol. Chem. 273: 34139–34144

  • Shen JC, Loeb LA . 2000 Trends Genet. 16: 213–220

  • Shiratori M, Sakamoto S, Suzuki N, Tokutake Y, Kawabe Y, Enomoto T, Sugimoto M, Goto M, Matsumoto T, Furuichi Y . 1999 J. Cell Biol. 144: 1–9

  • Sinclair DA, Mills K, Guarente L . 1997 Science 277: 1313–1316

  • Smider V, Rathmell WK, Lieber MR, Chu G . 1994 Science 266: 288–291

  • Smith SD, Oriahi E, Lowe D, Yang-Yen HF, O'Mahony D, Rose K, Chen K, Rothblum LI . 1990 Mol. Cell. Biol. 10: 3105–3116

  • Stein GH, Yanishevsky R . 1994 Meth. Enzymol. 58: 279–292

  • Suzuki N, Shimamoto A, Imamura O, Kuromitsu J, Kitao S, Goto M, Furuichi Y . 1997 Nucleic Acids Res. 25: 2973–2978

  • Suzuki T, Shiratori M, Furuichi Y, Matsumoto T . 2001 Oncogene 20: 2551–2558

  • Suzuki N, Shiratori M, Goto M, Furuichi Y . 1999 Nucleic Acids Res. 27: 2361–2368

  • Watt PM, Louis EJ, Borts RH, Hickson ID . 1995 Cell 81: 253–260

  • Watt PM, Hickson ID, Borts RH, Louis EJ . 1996 Genetics 144: 935–945

  • Yu C-E, Oshima J, Fu YH, Wijsman EM, Hisama F, Alisch R, Matthews S, Nakura J, Miki T, Ouais S, Martin GM, Mulligan J, Schellenberg GD . 1996 Science 272: 258–262

Download references

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.

Author information

Author notes

  1. Miwa Shiratori

    Present address: GenCom Corporation, 914 Minamiooya, Machida, Tokyo, 194-8511, Japan

Authors and Affiliations

  1. AGENE Research Institute, 200 Kajiwara, Kamukura, Kanagawa, 247-0063, Japan

    Miwa Shiratori, Takahisa Suzuki, Chie Itoh, Yasuhiro Furuichi & Takehisa Matsumoto

  2. Department of Rheumatology, Tokyo Metropolitan Otsuka Hospital, Minami-Otsuka, Toshima-Ku, Tokyo, 170-0005, Japan

    Makoto Goto

Authors
  1. Miwa Shiratori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takahisa Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chie Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Makoto Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasuhiro Furuichi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takehisa Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takehisa Matsumoto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205334

Keywords

This article is cited by

Search

Advanced search

Quick links