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Lipid is new Star in nuclear regulation

Knockdown of Star-PAP (green) or PIPKI- (red) reduces multiple stress response mRNAs. ANDERSON/MACMILLAN

Alipid known for its cytoplasmic duties jacks up mRNA levels by activating a polyadenylating enzyme, say Richard Anderson and colleagues (University of Wisconsin, Madison, WI).

The PtdIns4,5P₂ phosphoinositide is generated by PIPK-, which is activated by an as-yet uncharacterized stress–response pathway and which links to mRNA-processing complexes called nuclear speckles. In their new study, the authors used the enzyme's speckle-targeting region as bait to find PIPK-–associated proteins, which they reasoned might be regulatory targets of PtdIns4,5P₂. This strategy led them to a new polyadenylating enzyme they named "speckle-targeted PIPK-–regulated poly(A) polymerase," or Star-PAP. The close proximity of PIPK- and Star-PAP might facilitate the lipid's ability to turn on the polymerase.

A knockdown of either Star-PAP or PIPK- reduced the polyadenylation and subsequent expression levels of about 2,000 mRNAs, many of which are involved in response to oxidative stress. Treatment of cells with an oxidative stressor increased the association of Star-PAP with PIPK- and the RNA polymerase machinery and thereby increased Star-PAP's activity. Together, the data show the Star-PAP assembly is positioned to extend poly(A) tails on transcripts that are needed for surviving oxidative stresses.

"This is a novel gene expression regulatory mechanism," says Anderson. "It's also the first poly(A) polymerase [found to be] regulated by a signaling pathway. This suggests that other PAPs may be regulated as well."

Mellman, D.L., et al. 2008. Nature. 451:1013–1018.[CrossRef][Medline]

Richard Robinson

rrobinson{at}nasw.org

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This Article Full Text (PDF, 1027K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?