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 in | Molecular cell Vol. 49; no. 1; pp. 7 - 17 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
10.01.2013
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Subjects | |
Online Access | Get full text |
ISSN | 1097-2765 1097-4164 1097-4164 |
DOI | 10.1016/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.
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► 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 |
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Bibliography: | http://dx.doi.org/10.1016/j.molcel.2012.11.005 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 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 |