Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 6 April 2010
Vol. 3, Issue 116, p. ra27
[DOI: 10.1126/scisignal.2000468]

RESEARCH ARTICLES

AAA+ Proteins RUVBL1 and RUVBL2 Coordinate PIKK Activity and Function in Nonsense-Mediated mRNA Decay

Natsuko Izumi1, Akio Yamashita1,2,6*, Akihiro Iwamatsu3, Rie Kurata1, Hiroki Nakamura4, Bonnie Saari5, Hisashi Hirano4, Philip Anderson5, and Shigeo Ohno1,6*

1 Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan.
2 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
3 Protein Research Network Co., Ltd., Yokohama 236-0004, Japan.
4 International Graduate School of Arts and Sciences, Yokohama City University, Yokohama 230-0045, Japan.
5 Department of Genetics, University of Wisconsin, Madison, WI 53706, USA.
6 Advanced Medical Research Center, Yokohama City University, Yokohama 236-0004, Japan.

Abstract: Phosphatidylinositol 3-kinase–related protein kinase (PIKK) family proteins play essential roles in DNA-based and RNA-based processes, such as the response to DNA damage, messenger RNA (mRNA) quality control, transcription, and translation, where they contribute to the maintenance of genome integrity and accurate gene expression. The adenosine triphosphatases associated with diverse cellular activities (AAA+) family proteins RuvB-like 1 (RUVBL1) and RUVBL2 are involved in various cellular processes, including transcription, RNA modification, DNA repair, and telomere maintenance. We show that RUVBL1 and RUVBL2 associate with each PIKK family member. We also show that RUVBL1 and RUVBL2 control PIKK abundance at least at the mRNA level. Knockdown of RUVBL1 or RUVBL2 decreased PIKK abundance and impaired PIKK-mediated signaling. Analysis of SMG-1, a PIKK family member involved in nonsense-mediated mRNA decay (NMD), revealed an essential role for RUVBL1 and RUVBL2 in NMD. RUVBL1 and RUVBL2 associated with SMG-1 and the messenger ribonucleoproteins in the cytoplasm and promoted the formation of mRNA surveillance complexes during NMD. Thus, RUVBL1 and RUVBL2 regulate PIKK functions on two different levels: They control the abundance of PIKKs, and they stimulate the formation of PIKK-containing molecular complexes, such as those involved in NMD.

* To whom correspondence should be addressed. E-mail: ohnos{at}med.yokohama-cu.ac.jp (S.O.); yamasita{at}yokohama-cu.ac.jp (A.Y.)

Citation: N. Izumi, A. Yamashita, A. Iwamatsu, R. Kurata, H. Nakamura, B. Saari, H. Hirano, P. Anderson, S. Ohno, AAA+ Proteins RUVBL1 and RUVBL2 Coordinate PIKK Activity and Function in Nonsense-Mediated mRNA Decay. Sci. Signal. 3, ra27 (2010).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Chaperone-like activity of the AAA+ proteins Rvb1 and Rvb2 in the assembly of various complexes.
N. Nano and W. A. Houry (2013)
Phil Trans R Soc B 368, 20110399
   Abstract »    Full Text »    PDF »
The Emergence of the Conserved AAA+ ATPases Pontin and Reptin on the Signaling Landscape.
J. Rosenbaum, S. H. Baek, A. Dutta, W. A. Houry, O. Huber, T. R. Hupp, and P. M. Matias (2013)
Science Signaling 6, mr1
   Abstract »    Full Text »    PDF »
The ATPase Activity of Reptin Is Required for Its Effects on Tumor Cell Growth and Viability in Hepatocellular Carcinoma.
A. Grigoletto, V. Neaud, N. Allain-Courtois, P. Lestienne, and J. Rosenbaum (2013)
Mol. Cancer Res. 11, 133-139
   Abstract »    Full Text »    PDF »
Conformational transitions regulate the exposure of a DNA-binding domain in the RuvBL1-RuvBL2 complex.
A. Lopez-Perrote, H. Munoz-Hernandez, D. Gil, and O. Llorca (2012)
Nucleic Acids Res. 40, 11086-11099
   Abstract »    Full Text »    PDF »
Ubiquitin-specific Peptidase 9, X-linked (USP9X) Modulates Activity of Mammalian Target of Rapamycin (mTOR).
P. Agrawal, Y.-T. Chen, B. Schilling, B. W. Gibson, and R. E. Hughes (2012)
J. Biol. Chem. 287, 21164-21175
   Abstract »    Full Text »    PDF »
Vitrification at the pre-antral stage transiently alters inner mitochondrial membrane potential but proteome of in vitro grown and matured mouse oocytes appears unaffected.
M. Demant, T. Trapphoff, T. Frohlich, G. J. Arnold, and U. Eichenlaub-Ritter (2012)
Hum. Reprod. 27, 1096-1111
   Abstract »    Full Text »    PDF »
N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD.
Y. Okada-Katsuhata, A. Yamashita, K. Kutsuzawa, N. Izumi, F. Hirahara, and S. Ohno (2012)
Nucleic Acids Res. 40, 1251-1266
   Abstract »    Full Text »    PDF »
The nonsense-mediated mRNA decay SMG-1 kinase is regulated by large-scale conformational changes controlled by SMG-8.
E. Arias-Palomo, A. Yamashita, I. S. Fernandez, R. Nunez-Ramirez, Y. Bamba, N. Izumi, S. Ohno, and O. Llorca (2011)
Genes & Dev. 25, 153-164
   Abstract »    Full Text »    PDF »
Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex.
I. S. Fernandez, A. Yamashita, E. Arias-Palomo, Y. Bamba, R. A. Bartolome, M. A. Canales, J. Teixido, S. Ohno, and O. Llorca (2011)
Nucleic Acids Res. 39, 347-358
   Abstract »    Full Text »    PDF »
Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes.
H. Takai, Y. Xie, T. de Lange, and N. P. Pavletich (2010)
Genes & Dev. 24, 2019-2030
   Abstract »    Full Text »    PDF »
Tti1 and Tel2 Are Critical Factors in Mammalian Target of Rapamycin Complex Assembly.
T. Kaizuka, T. Hara, N. Oshiro, U. Kikkawa, K. Yonezawa, K. Takehana, S.-i. Iemura, T. Natsume, and N. Mizushima (2010)
J. Biol. Chem. 285, 20109-20116
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882