%0 Journal Article
%T Regulation of PURA gene transcription by three promoters generating distinctly spliced 5-prime leaders: a novel means of fine control over tissue specificity and viral signals
%A Margaret J Wortman
%A Laura K Hanson
%A Luis Mart¨ªnez-Sobrido
%A Ann E Campbell
%A Jonas A Nance
%A Adolfo Garc¨ªa-Sastre
%A Edward M Johnson
%J BMC Molecular Biology
%D 2010
%I BioMed Central
%R 10.1186/1471-2199-11-81
%X Here we report that human PURA (hPURA) transcription is regulated from three distinct and widely-separated transcription start sites (TSS). Each of these TSS is strongly homologous to a similar site in mouse chromosomal DNA. Transcripts from TSS I and II are characterized by the presence of large and overlapping 5'-UTR introns terminated at the same splice receptor site. Transfection of lung carcinoma cells with wild-type or mutated hPURA 5' upstream sequences identifies different regulatory elements. TSS III, located within 80 bp of the translational start codon, is upregulated by E2F1, CAAT and NF-Y binding elements. Transcription at TSS II is downregulated through the presence of adjacent consensus binding elements for interferon regulatory factors (IRFs). Chromatin immunoprecipitation reveals that IRF-3 protein binds hPURA promoter sequences at TSS II in vivo. By co-transfecting hPURA reporter plasmids with expression plasmids for IRF proteins we demonstrate that several IRFs, including IRF-3, down-regulate PURA transcription. Infection of NIH 3T3 cells with mouse cytomegalovirus results in a rapid decrease in levels of mPURA mRNA and Pur¦Á protein. The viral infection alters the degree of splicing of the 5'-UTR introns of TSS II transcripts.Results provide evidence for a novel mechanism of transcriptional control by multiple promoters used differently in various tissues and cells. Viral infection alters not only the use of PURA promoters but also the generation of different non-coding RNAs from 5'-UTRs of the resulting transcripts.The Pur protein family of sequence-specific single-stranded nucleic acid-binding proteins is extremely well conserved from bacteria through humans [1]. Human and mouse Pur¦Á differ by only 2 amino acids. Human family member, Pur¦Á, has a primitive codon usage preference resembling that in bacteria. Pur¦Á was first identified due to its ability to bind a purine-rich sequence in an initiation zone of DNA replication upstream of the c-MYC ge
%U http://www.biomedcentral.com/1471-2199/11/81