RT Journal Article
SR Electronic
T1 AAA+ Proteins RUVBL1 and RUVBL2 Coordinate PIKK Activity and Function in Nonsense-Mediated mRNA Decay
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra27
OP ra27
DO 10.1126/scisignal.2000468
VO 3
IS 116
A1 Izumi, Natsuko
A1 Yamashita, Akio
A1 Iwamatsu, Akihiro
A1 Kurata, Rie
A1 Nakamura, Hiroki
A1 Saari, Bonnie
A1 Hirano, Hisashi
A1 Anderson, Philip
A1 Ohno, Shigeo
YR 2010
UL http://stke.sciencemag.org/content/3/116/ra27.abstract
AB 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.