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

Abstract

In this study we identified a novel protein which may contribute to the transcriptional inactivity of Alu retroposons in vivo. A human cDNA clone encoding this protein (ACR1) was isolated from a human expression library using South-western screening with an Alu subfragment, implicated in the regulation of Alu in vitro transcription and interacting with a HeLa nuclear protein down-regulated in adenovirus-infected cells. Bacterially expressed ACR1 is demonstrated to inhibit RNA polymerase III (Pol III)-dependent Alu transcription 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 with a possible repressor function of the protein in vivo. ACR1 is mainly (but not exclusively) located in cytoplasm and appears to be a member of a weakly characterized redox protein family having a central, highly conserved sequence 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 protein cyclophilin, and mammalian cyclophilin A (an abundant ubiquitously expressed protein) is known to interact with human transcriptional repressor YY1, which is a major sequence-specific Alu-binding protein in human cells. It appears, therefore, that transcriptional silencing of Alu in vivo is a result of complex interactions of many proteins which bind to its Pol III promoter.

Regulation of BRCA2 Gene Expression by the SLUG Repressor Protein in Human Breast Cells

“…Many Alu sequences are transcribed by RNA polymerase III, and this transcription is regulated by many RNA polymerase III transcription factors (20). One of these factors is an ϳ23-kDa Alu-co-repressor protein ACR1 (20).…”

“…ACR1 protein may still bind to it and mediate the masking of the E2-box from being bound by SLUG repressor protein. Apart from ACR1, the polymerase II transcription factor YY1 may also bind to the same sequence of the Alu element (20,28) and thus, has the potential to add to the desilencing mechanism.…”

“…1, A and B). This inter-Alu sequence houses an E2-box sequence (5Ј-CACCTG-3Ј) as well as a 63-bp patch overlapping the E2-box that has Ͼ83% identity with the footprint of a RNA polymerase III transcriptional regulator ACR1 (20) (Fig. 1, A and B).…”

Crystal Structure of a Dimeric Oxidized form of Human Peroxiredoxin 5

“…7,10 PRDX5, previously named PrxV, AOEB166, PMP20 or ACR1, is the last member of mammalian PRDXs that has been cloned and characterized. 12,[18][19][20][21][22] Human PRDX5 can be addressed to several subcellular compartments such as mitochondria, peroxisomes, the nucleus and the cytosol. 12,[18][19][20][21] In a previous report, we presented a crystal structure of human PRDX5 in its reduced form.…”

“…12,[18][19][20][21][22] Human PRDX5 can be addressed to several subcellular compartments such as mitochondria, peroxisomes, the nucleus and the cytosol. 12,[18][19][20][21] In a previous report, we presented a crystal structure of human PRDX5 in its reduced form. 22 The structure revealed that peroxidatic Cys47 and resolving Cysl51 were too distant to form an intramolecular disulfide bond upon oxidation without important conformational changes.…”