A novel human DNA-binding protein with sequence similarity to a subfamily of redox proteins which is able to repress RNA-polymerase-III-driven transcription of the Alu-family retroposons in vitro

In this study we identified a novel protein which may contribute to the tra nscriptional inactivity of Alu retroposons in vivo. A human cDNA clone enco ding this protein (ACR1) was isolated from a human expression library using South-western screening with an Alu subfragment, implicated in the regulat ion of Alu in vitro transcription and interacting with a HeLa nuclear prote in down-regulated in adenovirus-infected cells. Bacterially expressed ACR1 is demonstrated to inhibit RNA polymerase III (Pol III)-dependent Alu trans cription in vitro but showed no repression of transcription of a tRNA gene or of a reporter gene under control of a Pol ii promoter ACR1 mRNA is also found to be down-regulated in adenovirus-infected HeLa cells, consistent wi th a possible repressor function of the protein in vivo. ACR1 is mainly (bu t not exclusively) located in cytoplasm and appears to be a member of a wea kly characterized redox protein family having a central, highly conserved s equence motif, PGAFTPXCXXXXLP. One member of the family identified earlier as peroxisomal membrane protein (PMP)20 is known to interact in a sequence- specific manner with a yeast homolog of mammalian cyclosporin-A-binding pro tein cyclophilin, and mammalian cyclophilin A (an abundant ubiquitously exp ressed protein) is known to interact with human transcriptional repressor Y Y1, which is a major sequence-specific Alu-binding protein in human cells. It appears, therefore, that transcriptional silencing of Alu-binding is a r esult of complex interactions of many proteins which bind to its Pol III pr omoter.