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Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2015 Aug 18; Vol. 43 (14), pp. 7005-20. Date of Electronic Publication: 2015 Jul 02. - Publication Year :
- 2015
-
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 PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα 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.<br /> (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Subjects :
- Casein Kinase I metabolism
Cell Nucleus enzymology
HEK293 Cells
HeLa Cells
Humans
Nucleotidyltransferases
Oxidative Stress
Phosphatidylinositol 4,5-Diphosphate metabolism
Phosphorylation
Polynucleotide Adenylyltransferase chemistry
Protein Binding
Serine metabolism
Signal Transduction
Zinc Fingers
Phosphotransferases (Alcohol Group Acceptor) metabolism
Polynucleotide Adenylyltransferase metabolism
RNA 3' End Processing
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 43
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 26138484
- Full Text :
- https://doi.org/10.1093/nar/gkv676