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Genes Dev. 2008 Feb 15;22(4):499-511. doi: 10.1101/gad.1628208.

Sumoylation regulates multiple aspects of mammalian poly(A) polymerase function.

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  • 1Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Abstract

The addition of the poly(A) tail to the ends of eukaryotic mRNAs is catalyzed by poly(A) polymerase (PAP). PAP activity is known to be highly regulated, for example, by alternative splicing and phosphorylation. In this study we show that the small ubiquitin-like modifier (SUMO) plays multiple roles in regulating PAP function. Our discovery of SUMO-conjugated PAP began with the observation of a striking pattern of abundant higher-molecular-weight forms of PAP in certain mouse tissues and cell lines. PAP constitutes an unusual SUMO substrate in that, despite the absence of any consensus sumoylation sites, PAP interacts very strongly with the SUMO E2 enzyme ubc9 and can be extensively sumoylated both in vitro and in vivo. Six sites of sumoylation in PAP were identified, with two overlapping one of two nuclear localization signals (NLS). Strikingly, mutation of the two lysines at the NLS to arginines, or coexpression of a SUMO protease with wild-type PAP, caused PAP to be localized to the cytoplasm, demonstrating that sumoylation is required to facilitate PAP nuclear localization. Sumoylation also contributes to PAP stability, as down-regulation of sumoylation led to decreases in PAP levels. Finally, the activity of purified PAP was shown to be inhibited by in vitro sumoylation. Our study thus shows that SUMO regulates PAP in numerous distinct ways and is integral to normal PAP function.

PMID:
18281463
[PubMed - indexed for MEDLINE]
PMCID:
PMC2238671
Free PMC Article

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