title: Polypyrimidine tract binding protein (hnRNP I) is possibly a conserved modulator of miRNA-mediated gene regulation.
abstract: MiRNAs can regulate gene expression through versatile mechanisms that result in increased or decreased expression of the targeted mRNA and it could effect the expression of thousands of protein in a particular cell. An increasing body of evidence suggest that miRNAs action can be modulated by proteins that bind to the same 3'UTRs that are targeted by miRNAs, suggesting that other factors apart from miRNAs and their target sites determine miRNA-modulation of gene expression. We applied an affinity purification protocol using biotinylated let-7 miRNA inhibitor to isolate proteins that are involved in let-7 mediated gene regulation that resulted in an affinity purification of Polypyrimidine Tract Binding protein (PTB). Here we show that PTB interacts with miRNAs and human Argonaute 2 (hAgo2) through RNA as well as identified potential mammalian cellular targets that are co-regulated by PTB and hAgo2. In addition, using genetic approach, we have demonstrated that PTB genetically interacts with Caenorhabditis elegans let-7 indicating a conserved role for PTB in miRNA-mediated gene regulation.
authors.affiliation: Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Bart
authors.initials: B
authors.lastname: Engels
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jannot
authors.forename: Judit
authors.initials: J
authors.lastname: Remenyi
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Simard
authors.forename: György
authors.initials: G
authors.lastname: Hutvagner
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D001483:Base Sequence; D017173:Caenorhabditis elegans; D002846:Chromatography, Affinity; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; C474488:let-7 microRNA, C elegans; C487931:mirnlet7 microRNA, human; D038941:Polypyrimidine Tract-Binding Protein