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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).

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