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Phosphorylation regulates the Star-PAP-PIPKI? interaction and directs specificity toward mRNA targets.


ABSTRACT: Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKI? interaction. We show that S6 is phosphorylated by CKI? within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKI?. Unlike the CKI? mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKI? activity. S6 phosphorylation together with coactivator PIPKI? controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3'-end processing.

SUBMITTER: Mohan N 

PROVIDER: S-EPMC4538844 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets.

Mohan Nimmy N   Sudheesh A P AP   Francis Nimmy N   Anderson Richard R   Laishram Rakesh S RS  

Nucleic acids research 20150702 14


Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these intera  ...[more]

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