Chapman Erich G, Hostetter Alethia A, Osborn Maire F, Miller Amanda L, DeRose Victoria J
Department of Chemistry, University of Oregon, Eugene, OR 97403, USA.
Met Ions Life Sci. 2011;9:347-77. doi: 10.1039/9781849732512-00347.
In this chapter several aspects of Pt(II) are highlighted that focus on the properties of Pt(II)-RNA adducts and the possibility that they influence RNA-based processes in cells. Cellular distribution of Pt(II) complexes results in significant platination of RNA, and localization studies find Pt(II) in the nucleus, nucleolus, and a distribution of other sites in cells. Treatment with Pt(II) compounds disrupts RNA-based processes including enzymatic processing, splicing, and translation, and this disruption may be indicative of structural changes to RNA or RNA-protein complexes. Several RNA-Pt(II) adducts have been characterized in vitro by biochemical and other methods. Evidence for Pt(II) binding in non-helical regions and for Pt(II) cross-linking of internal loops has been found. Although platinated sites have been identified, there currently exists very little in the way of detailed structural characterization of RNA-Pt(II) adducts. Some insight into the details of Pt(II) coordination to RNA, especially RNA helices, can be gained from DNA model systems. Many RNA structures, however, contain complex tertiary folds and common, purine-rich structural elements that present suitable Pt(II) nucleophiles in unique arrangements which may hold the potential for novel types of platinum-RNA adducts. Future research aimed at structural characterization of platinum-RNA adducts may provide further insights into platinum-nucleic acid binding motifs, and perhaps provide a rationale for the observed inhibition by Pt(II) complexes of splicing, translation, and enzymatic processing.
在本章中，重点介绍了Pt(II)的几个方面，这些方面聚焦于Pt(II)-RNA加合物的性质以及它们影响细胞中基于RNA的过程的可能性。Pt(II)配合物的细胞分布导致RNA发生显著的铂化，定位研究在细胞核、核仁以及细胞中其他一些位点发现了Pt(II)。用Pt(II)化合物处理会破坏基于RNA的过程，包括酶促加工、剪接和翻译，这种破坏可能表明RNA或RNA-蛋白质复合物发生了结构变化。几种RNA-Pt(II)加合物已通过生化和其他方法在体外进行了表征。已发现Pt(II)在非螺旋区域结合以及在内部环进行Pt(II)交联的证据。尽管已经确定了铂化位点，但目前对于RNA-Pt(II)加合物的详细结构表征还非常少。从DNA模型系统中可以获得一些关于Pt(II)与RNA（尤其是RNA螺旋）配位细节的见解。然而，许多RNA结构包含复杂的三级折叠和常见的富含嘌呤的结构元件，这些元件以独特的排列方式呈现出合适的Pt(II)亲核试剂，这可能为新型铂-RNA加合物提供了潜力。旨在对铂-RNA加合物进行结构表征的未来研究可能会进一步深入了解铂-核酸结合基序，也许还能为观察到的Pt(II)配合物对剪接、翻译和酶促加工的抑制作用提供理论依据。
