title: Cooperation meets competition in microRNA-mediated DMPK transcript regulation.
abstract: The fundamental role of microRNAs (miRNAs) in the regulation of gene expression has been well-established, but many miRNA-driven regulatory mechanisms remain elusive. In the present study, we demonstrate that miRNAs regulate the expression of DMPK, the gene mutated in myotonic dystrophy type 1 (DM1), and we provide insight regarding the concerted effect of the miRNAs on the DMPK target. Specifically, we examined the binding of several miRNAs to the DMPK 3' UTR using luciferase assays. We validated the interactions between the DMPK transcript and the conserved miR-206 and miR-148a. We suggest a possible cooperativity between these two miRNAs and discuss gene targeting by miRNA pairs that vary in distance between their binding sites and expression profiles. In the same luciferase reporter system, we showed miR-15b/16 binding to the non-conserved CUG repeat tract present in the DMPK transcript and that the CUG-repeat-binding miRNAs might also act cooperatively. Moreover, we detected miR-16 in cytoplasmic foci formed by exogenously expressed RNAs with expanded CUG repeats. Therefore, we propose that the expanded CUGs may serve as a target for concerted regulation by miRNAs and may also act as molecular sponges for natural miRNAs with CAG repeats in their seed regions, thereby affecting their physiological functions.
authors: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland edytak@ibch.poznan.pl.
authors: Edyta
authors: E
authors: Koscianska
authors: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
authors: Tomasz M
authors: TM
authors: Witkos
authors: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
authors: Emilia
authors: E
authors: Kozlowska
authors: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
authors: Marzena
authors: M
authors: Wojciechowska
authors: Department of Molecular Biomedicine, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland wlodkrzy@ibch.poznan.pl.
authors: Wlodzimierz J
authors: WJ
authors: Krzyzosiak
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D065636:Myotonin-Protein Kinase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D018911:Trinucleotide Repeats
chemical_list: D020413:3' Untranslated Regions; C585517:DMPK protein, human; C550570:MIRN148 microRNA, human; C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D065636:Myotonin-Protein Kinase