Regulation of Pur? gene transcription: Evidence for autoregulation of Pur? promoter

Muralidharan, Vandhana; Sweet, Thersa; Nadraga, Yuri; Amini, Shohreh; Khalili, Kamel

doi:10.1002/1097-4652(2000)9999:999<000::aid-jcp1039>3.0.co;2-p

Cited by 10 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two TSSs as determined from ESTs are shown for mouse. The one most distant from ATG has previously been identified [28]. The new mouse TSS is very homologous to human TSS III, which is verified in this report.…”

Section: Resultssupporting

confidence: 85%

“…The discrete nature of these length groups indicates that each corresponds to a separate transcriptional start site (TSS). The 5' ends of the transcripts in TSS I, located most distant from the translational start codon, correspond to the only thus-far-demonstrated mouse TSS [27,28]. The sequence surrounding this TSS is strongly conserved in mouse and humans (Additional file 1, Figure S1) and is, therefore, likely to be a human TSS.…”

Section: Resultsmentioning

confidence: 99%

“…In both species this intron is completely within the 5'-UTR. It is not extensively analyzed here, as it has already been analyzed in the mouse [28]. …”

Section: Resultsmentioning

confidence: 99%

“…Human PURA TSS I is furthest upstream of the translational start site. Because its promoter is very homologous to a previously characterized mouse promoter [28], we have not further studied it here. In the mouse, this TSS I promoter is notably subject to feedback regulation by the Purα protein [28].…”

Section: Discussionmentioning

confidence: 99%

“…Because its promoter is very homologous to a previously characterized mouse promoter [28], we have not further studied it here. In the mouse, this TSS I promoter is notably subject to feedback regulation by the Purα protein [28]. Human TSS II is adjacent to an intriguing cluster of elements potentially involved in an innate immune response to viral infection.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

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

et al. 2010

View full text Add to dashboard Cite

BackgroundPurα is an evolutionarily conserved cellular protein participating in processes of DNA replication, transcription, and RNA transport; all involving binding to nucleic acids and altering conformation and physical positioning. The distinct but related roles of Purα suggest a need for expression regulated differently depending on intracellular and external signals.ResultsHere 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 Purα protein. The viral infection alters the degree of splicing of the 5'-UTR introns of TSS II transcripts.ConclusionsResults 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.

show abstract

Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

“…In both species this intron is completely within the 5'-UTR. It is not extensively analyzed here, as it has already been analyzed in the mouse [28]. …”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2010

View full text Add to dashboard Cite

show abstract

Regulation of the Pur-alpha promoter by E2F-1

Darbinian¹,

White²,

Khalili³

2006

J. Cell. Biochem.

Self Cite

View full text Add to dashboard Cite

Puralpha is a ubiquitously expressed multifunctional nucleic acid-binding protein that is involved in many cellular processes including transcriptional regulation, the cell cycle, oncogenic transformation, and post-natal brain development. Previously, Puralpha protein was found to bind to E2F-1, inhibit E2F-1 transcriptional activity, and reverse the effects of ectopic E2F-1 expression on cell growth. Also Puralpha binds to a GC/GA-rich sequence within its own promoter and inhibits gene expression, that is, Puralpha is autoregulated. We now report that the Puralpha promoter (pPuralpha) is induced by E2F-1 and that this activity maps to a consensus E2F-1 binding motif that is juxtaposed to the Puralpha binding site. Deletion mutants of the E2F-1 protein showed that the region between amino acid residues 88-241 is important for this activity. E2F-1-associated activation of the pPuralpha was inhibited by co-expression of Puralpha, pRb, and an RNA species with specific binding to E2F-1. Chromatin immunoprecipitation (ChIP) assay using primers that flanked the juxtaposed Puralpha and E2F-1 binding sites verified the presence of Puralpha and E2F-1 on the pPuralpha in vivo. In a Tet-inducible cell line, Puralpha delayed cell cycle progression. Thus, E2F-1 and Puralpha interplay appears to be involved in the regulation of Puralpha expression and the cell cycle.

show abstract

PURA , the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions

Daniel

Johnson

2018

Gene

View full text Add to dashboard Cite

The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1 to 4 PUR family members. Human PUR genes encode Pur-alpha (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein that binds specific DNA and RNA sequence elements. Human PURA, located at chromosome band 5q31, is under complex control of three promoters. The entire protein coding sequence of PURA is contiguous within a single exon. Several studies have found that overexpression or microinjection of Pura inhibits anchorage-independent growth of oncogenically transformed cells and blocks proliferation at either G1-S or G2-M checkpoints. Effects on the cell cycle may be mediated by interaction of Pura with cellular proteins including Cyclin/Cdk complexes and the Rb tumor suppressor protein. PURA knockout mice die shortly after birth with effects on brain and hematopoietic development. In humans environmentally induced heterozygous deletions of PURA have been implicated in forms of myelodysplastic syndrome and progression to acute myelogenous leukemia. Pura plays a role in AIDS through association with the HIV-1 protein, Tat. In the brain Tat and Pura association in glial cells activates transcription and replication of JC polyomavirus, the agent causing the demyelination disease, progressive multifocal leukoencephalopathy. Tat and Pura also act to stimulate replication of the HIV-1 RNA genome. In neurons Pura accompanies mRNA transcripts to sites of translation in dendrites. Microdeletions in the PURA locus have been implicated in several neurological disorders. De novo PURA mutations have been related to a spectrum of phenotypes indicating a potential PURA syndrome. The nucleic acid, G-rich Pura binding element is amplified as expanded polynucleotide repeats in several brain diseases including fragile X syndrome and a familial form of amyotrophic lateral sclerosis/fronto-temporal dementia. Throughout evolution the Pura protein plays a critical role in survival, based on conservation of its nucleic acid binding properties. These Pura properties have been adapted in higher organisms to the as yet unfathomable development of the human brain.

show abstract

Regulation of Pur? gene transcription: Evidence for autoregulation of Pur? promoter

Cited by 10 publications

References 20 publications

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

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

Regulation of the Pur-alpha promoter by E2F-1

PURA , the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions

Contact Info

Product

Resources

About