Multiple roles for Purα in cellular and viral regulation

Pur-alpha is a ubiquitous multifunctional protein that is strongly conserved throughout evolution, binds to both DNA and RNA and functions in the initiation of DNA replication, control of transcription and mRNA translation. In addition, it binds to several cellular regulatory proteins including the retinoblastoma protein, E2F-1, Sp1, YB-1, cyclin T1/Cdk9 and cyclin A/Cdk2. These observations and functional studies provide evidence that Pur alpha is a major player in the regulation of the cell cycle and oncogenic transformation. Pur alpha also binds to viral proteins such as the large T-antigen of JC virus (JCV) and the Tat protein of human immunodeficiency virus-1 (HIV-1) and plays a role in the cross-communication of these viruses in the opportunistic polyomavirus JC (JCV) brain infection, progressive multifocal leukoencephalopathy (PML). The creation of transgenic mice with inactivation of the PURA gene that encodes Pur alpha has revealed that Pur alpha is critical for postnatal brain development and has unraveled an essential role of Pur alpha in the transport of specific mRNAs to the dendrites and the establishment of the postsynaptic compartment in the developing neurons. Finally, the availability of cell cultures from the PURA knockout mice has allowed studies that have unraveled a role for Pur alpha in DNA repair.