PMID- 26138484 OWN - NLM STAT- MEDLINE DCOM- 20151124 LR - 20211203 IS - 1362-4962 (Electronic) IS - 0305-1048 (Print) IS - 0305-1048 (Linking) VI - 43 IP - 14 DP - 2015 Aug 18 TI - Phosphorylation regulates the Star-PAP-PIPKIalpha interaction and directs specificity toward mRNA targets. PG - 7005-20 LID - 10.1093/nar/gkv676 [doi] AB - 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 PIPKIalpha interaction. We show that S6 is phosphorylated by CKIalpha within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIalpha. Unlike the CKIalpha mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIalpha activity. S6 phosphorylation together with coactivator PIPKIalpha 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. CI - (c) The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. FAU - Mohan, Nimmy AU - Mohan N AD - Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Poojappura, Trivandrum 695014, India. FAU - Sudheesh, A P AU - Sudheesh AP AD - Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Poojappura, Trivandrum 695014, India. FAU - Francis, Nimmy AU - Francis N AD - Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Poojappura, Trivandrum 695014, India. FAU - Anderson, Richard AU - Anderson R AD - School of Medicine and Public Health, University of Wisconsin-Madison, WI 53706, USA. FAU - Laishram, Rakesh S AU - Laishram RS AD - Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud Post, Poojappura, Trivandrum 695014, India laishram@rgcb.res.in. LA - eng GR - IA/I/12/1/500508/WTDBT_/DBT-Wellcome Trust India Alliance/India GR - R01 GM051968/GM/NIGMS NIH HHS/United States GR - R35 GM134955/GM/NIGMS NIH HHS/United States GR - IA/I/1/505008/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150702 PL - England TA - Nucleic Acids Res JT - Nucleic acids research JID - 0411011 RN - 0 (Phosphatidylinositol 4,5-Diphosphate) RN - 0 (RNA, Messenger) RN - 452VLY9402 (Serine) RN - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)) RN - EC 2.7.1.68 (1-phosphatidylinositol-4-phosphate 5-kinase) RN - EC 2.7.11.1 (Casein Kinase I) RN - EC 2.7.7.- (Nucleotidyltransferases) RN - EC 2.7.7.- (TUT1 protein, human) RN - EC 2.7.7.19 (Polynucleotide Adenylyltransferase) SB - IM MH - Casein Kinase I/metabolism MH - Cell Nucleus/enzymology MH - HEK293 Cells MH - HeLa Cells MH - Humans MH - Nucleotidyltransferases MH - Oxidative Stress MH - Phosphatidylinositol 4,5-Diphosphate/metabolism MH - Phosphorylation MH - Phosphotransferases (Alcohol Group Acceptor)/*metabolism MH - Polynucleotide Adenylyltransferase/chemistry/*metabolism MH - Protein Binding MH - *RNA 3' End Processing MH - RNA, Messenger/*metabolism MH - Serine/metabolism MH - Signal Transduction MH - Zinc Fingers PMC - PMC4538844 EDAT- 2015/07/04 06:00 MHDA- 2015/12/15 06:00 PMCR- 2015/07/02 CRDT- 2015/07/04 06:00 PHST- 2015/06/19 00:00 [accepted] PHST- 2015/01/28 00:00 [received] PHST- 2015/07/04 06:00 [entrez] PHST- 2015/07/04 06:00 [pubmed] PHST- 2015/12/15 06:00 [medline] PHST- 2015/07/02 00:00 [pmc-release] AID - gkv676 [pii] AID - 10.1093/nar/gkv676 [doi] PST - ppublish SO - Nucleic Acids Res. 2015 Aug 18;43(14):7005-20. doi: 10.1093/nar/gkv676. Epub 2015 Jul 2.