PARP1 Represses PAP and Inhibits Polyadenylation during Heat Shock

The 3′ ends of most eukaryotic mRNAs are produced by an endonucleolytic cleavage followed by synthesis of a poly(A) tail. Poly(A) polymerase (PAP), the enzyme that catalyzes the formation of the tail, is subject to tight regulation involving several posttranslational modifications. Here we show that...

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Published inMolecular cell Vol. 49; no. 1; pp. 7 - 17
Main Authors Di Giammartino, Dafne Campigli, Shi, Yongsheng, Manley, James L.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 10.01.2013
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ISSN1097-2765
1097-4164
1097-4164
DOI10.1016/j.molcel.2012.11.005

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Summary:The 3′ ends of most eukaryotic mRNAs are produced by an endonucleolytic cleavage followed by synthesis of a poly(A) tail. Poly(A) polymerase (PAP), the enzyme that catalyzes the formation of the tail, is subject to tight regulation involving several posttranslational modifications. Here we show that the enzyme poly(ADP-ribose) polymerase 1 (PARP1) modifies PAP and regulates its activity both in vitro and in vivo. PARP1 binds to and modifies PAP by poly(ADP-ribosyl)ation (PARylation) in vitro, which inhibits PAP activity. In vivo we show that PAP is PARylated during heat shock, leading to inhibition of polyadenylation in a PARP1-dependent manner. The observed inhibition reflects reduced RNA binding affinity of PARylated PAP in vitro and decreased PAP association with non-heat shock protein-encoding genes in vivo. Our results provide direct evidence that PARylation can control processing of mRNA precursors, and also identify PARP1 as a regulator of polyadenylation during thermal stress. [Display omitted] ► PARP1 binds and PARylates PAP in vitro, which inhibits its polyadenylation activity ► Polyadenylation is inhibited during heat shock in a PARP1-dependent manner ► PAP is PARylated in vivo during heat shock ► Inhibition of polyadenylation reflects decreased RNA binding by PARylated PAP
Bibliography:http://dx.doi.org/10.1016/j.molcel.2012.11.005
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Current address: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.
ISSN:1097-2765
1097-4164
1097-4164
DOI:10.1016/j.molcel.2012.11.005