title: MicroRNA-130a associates with ribosomal protein L11 to suppress c-Myc expression in response to UV irradiation.
abstract: The oncoprotein c-Myc is essential for cell growth and proliferation while its deregulated overexpression is associated with most human cancers. Thus tightly regulated levels and activity of c-Myc are critical for maintaining normal cell homeostasis. c-Myc is down-regulated in response to several types of stress, including UV-induced DNA damage. Yet, mechanism underlying UV-induced c-Myc reduction is not completely understood. Here we report that L11 promotes miR-130a targeting of c-myc mRNA to repress c-Myc expression in response to UV irradiation. miR-130a targets the 3'-untranslated region (UTR) of c-myc mRNA. Overexpression of miR-130a promotes the Ago2 binding to c-myc mRNA, significantly reduces the levels of both c-Myc protein and mRNA and inhibits cell proliferation. UV treatment markedly promotes the binding of L11 to miR-130a, c-myc mRNA as well as Ago2 in cells. Inhibiting miR-130a significantly suppresses UV-mediated c-Myc reduction. We further show that L11 is relocalized from the nucleolus to the cytoplasm where it associates with c-myc mRNA upon UV treatment. Together, these results reveal a novel mechanism underlying c-Myc down-regulation in response to UV-mediated DNA damage, wherein L11 promotes miR-130a-loaded miRISC to target c-myc mRNA.
authors.affiliation: Departments of Molecular & Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Yuhuang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Departments of Molecular & Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Kishore B
authors.initials: KB
authors.lastname: Challagundla
authors.affiliation: Departments of Molecular & Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Sun
authors.affiliation: Department of Dermatology, University of Colorado, Denver, Aurora, CO 80045, USA.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Departments of Molecular & Medical Genetics, School of Medicine and the OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Mu-Shui
authors.initials: MS
authors.lastname: Dai
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000528:radiation effects; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects*; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D020413:3' Untranslated Regions; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012269:Ribosomal Proteins; C027624:ribosomal protein L11