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

Sci. Signal.  06 Apr 2010:
Vol. 3, Issue 116, pp. ra27
DOI: 10.1126/scisignal.2000468

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Masters of Integrity

In order to survive and faithfully reproduce, cells must not only maintain the integrity of their genome but also regulate the expression of the encoded products, ensure the quality of the transcripts, and coordinate protein production with metabolic status. Members of the phosphatidylinositol 3-kinase–related protein kinase (PIKK) family play essential roles in the DNA- and RNA-based processes that ensure genome integrity and accurate gene expression. Izumi et al. show that the two members of the AAA+ family of proteins, RUVBL1 and RUVBL2, which form a complex involved in chromatin-based processes, also regulated the activity and abundance of all members of the PIKK family. Furthermore, through an interaction with the PIKK member SMG-1, RUVBL1 and RUVBL2 contributed to the formation of macromolecular complexes involved in nonsense-mediated decay, a process by which prematurely terminated mRNA transcripts are eliminated to ensure that potentially dangerous truncated proteins are not produced.

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