Nonspecific Binding of RNA to PARP1 and PARP2 Does Not Lead to Catalytic Activation.,Biochemistry

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Nonspecific Binding of RNA to PARP1 and PARP2 Does Not Lead to Catalytic Activation.
Biochemistry ( IF 2.9 ) Pub Date : 2019-12-16 , DOI: 10.1021/acs.biochem.9b00986
Meagan Y Nakamoto ₁ , Johannes Rudolph ₁ , Deborah S Wuttke ₁ , Karolin Luger _{1,

2}

Affiliation

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2, respectively), upon binding damaged DNA, become activated to add long chains of poly(ADP-ribose) (PAR) to themselves and other nuclear proteins. This activation is an essential part of the DNA damage response. The PAR modifications recruit the DNA repair machinery to sites of DNA damage and result in base excision and single-strand break repair, homologous recombination, nucleotide excision repair, and alternative nonhomologous end joining. More recently, both PARP1 and PARP2 have been shown to bind to or be activated by RNA, a property that could interfere with the function of PARP1 and PARP2 in the response to DNA damage or lead to necrosis by depletion of cellular NAD+. We have quantitatively evaluated the in vitro binding of a variety of RNAs to PARP1 and PARP2 and queried the ability of these RNAs to switch on enzymatic activity. We find that while both proteins bind RNAs without specificity toward sequence or structure, their interaction with RNA does not lead to auto-PARylation. Thus, although PARP1 and PARP2 are promiscuous with respect to activation by DNA, they both demonstrate exquisite selectivity against activation by RNA.

中文翻译：

RNA 与 PARP1 和 PARP2 的非特异性结合不会导致催化激活。

聚（ADP-核糖）聚合酶 1 和 2（分别为 PARP1 和 PARP2）在与受损 DNA 结合后被激活，将聚（ADP-核糖）（PAR）的长链添加到自身和其他核蛋白中。这种激活是 DNA 损伤反应的重要组成部分。PAR 修饰将 DNA 修复机制招募到 DNA 损伤位点，并导致碱基切除和单链断裂修复、同源重组、核苷酸切除修复和替代的非同源末端连接。最近，已显示 PARP1 和 PARP2 都与 RNA 结合或被 RNA 激活，这种特性可能会干扰 PARP1 和 PARP2 在对 DNA 损伤的反应中的功能，或通过耗尽细胞 NAD+ 导致坏死。我们定量评估了各种 RNA 与 PARP1 和 PARP2 的体外结合，并询问了这些 RNA 开启酶活性的能力。我们发现，虽然这两种蛋白质结合 RNA 对序列或结构没有特异性，但它们与 RNA 的相互作用不会导致自动 PARylation。因此，尽管 PARP1 和 PARP2 在 DNA 激活方面是混杂的，但它们都表现出对 RNA 激活的极好的选择性。

更新日期：2019-12-17

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