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The prion protein gene: Identifying regulatory signals using marsupial sequence

Premzl, Marko; Delbridge, Margaret; Gready, Jill; Wilson, Peter; Johnson, Matthew; Davis, John; Kuczek, Elizabeth; Graves, Jennifer

Description

The function of the prion protein gene (PRNP) and its normal product PrPC is elusive. We used comparative genomics as a strategy to understand the normal function of PRNP. As the reliability of comparisons increases with the number of species and increased evolutionary distance, we isolated and sequenced a 66.5 kb BAC containing the PRNP gene from a distantly related mammal, the model Australian marsupial Macropus eugenii (tammar wallaby). Marsupials are separated from eutherians such as human...[Show more]

dc.contributor.authorPremzl, Marko
dc.contributor.authorDelbridge, Margaret
dc.contributor.authorGready, Jill
dc.contributor.authorWilson, Peter
dc.contributor.authorJohnson, Matthew
dc.contributor.authorDavis, John
dc.contributor.authorKuczek, Elizabeth
dc.contributor.authorGraves, Jennifer
dc.date.accessioned2015-12-13T22:43:35Z
dc.identifier.issn0378-1119
dc.identifier.urihttp://hdl.handle.net/1885/79259
dc.description.abstractThe function of the prion protein gene (PRNP) and its normal product PrPC is elusive. We used comparative genomics as a strategy to understand the normal function of PRNP. As the reliability of comparisons increases with the number of species and increased evolutionary distance, we isolated and sequenced a 66.5 kb BAC containing the PRNP gene from a distantly related mammal, the model Australian marsupial Macropus eugenii (tammar wallaby). Marsupials are separated from eutherians such as human and mouse by roughly 180 million years of independent evolution. We found that tammar PRNP, like human PRNP, has two exons. Prion proteins encoded by the tammar wallaby and a distantly related marsupial, Monodelphis domestica (Brazilian opossum) PRNP contain proximal PrP repeats with a distinct, marsupial-specific composition and a variable number. Comparisons of tammar wallaby PRNP with PRNPs from human, mouse, bovine and ovine allowed us to identify non-coding gene regions conserved across the marsupial-eutherian evolutionary distance, which are candidates for regulatory regions. In the PRNP 3′ UTR we found a conserved signal for nuclear-specific polyadenylation and the putative cytoplasmic polyadenylation element (CPE), indicating that post-transcriptional control of PRNP mRNA activity is important. Phylogenetic footprinting revealed conserved potential binding sites for the MZF-1 transcription factor in both upstream promoter and intron/intron 1, and for the MEF2, MyT1, Oct-1 and NFAT transcription factors in the intron(s). The presence of a conserved NFAT-binding site and CPE indicates involvement of PrPC in signal transduction and synaptic plasticity.
dc.publisherElsevier
dc.sourceGene
dc.subjectKeywords: cytoplasmic polyadenylation element binding protein; messenger RNA; myelin transcription factor 1; myeloid zinc finger 1; myocyte enhancer factor 2; octamer transcription factor 1; prion protein; transcription factor; transcription factor MyT1; transcript 3? untranslated region; Comparative genomics; Phylogenetic footprinting; Prion protein; Prion protein gene; Signal transduction; Synaptic plasticity; Transcription factors
dc.titleThe prion protein gene: Identifying regulatory signals using marsupial sequence
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume349
dc.date.issued2005
local.identifier.absfor060407 - Genome Structure and Regulation
local.identifier.absfor060409 - Molecular Evolution
local.identifier.absfor060405 - Gene Expression (incl. Microarray and other genome-wide approaches)
local.identifier.ariespublicationMigratedxPub7739
local.type.statusPublished Version
local.contributor.affiliationPremzl, Marko, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationDelbridge, Margaret, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationGready, Jill, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWilson, Peter, University of Queensland
local.contributor.affiliationJohnson, Matthew, University of Queensland
local.contributor.affiliationDavis, John, University of Queensland
local.contributor.affiliationKuczek, Elizabeth, University of Queensland
local.contributor.affiliationGraves, Jennifer, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage121
local.bibliographicCitation.lastpage134
local.identifier.doi10.1016/j.gene.2004.11.049
dc.date.updated2015-12-11T10:13:11Z
local.identifier.scopusID2-s2.0-17044378114
CollectionsANU Research Publications

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