title: Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation.
abstract: (A+U)-rich elements (AREs) within 3' untranslated regions are signals for rapid degradation of messenger RNAs encoding many oncoproteins and cytokines. The ARE-binding protein AUF1 contributes to their degradation. We identified MYC proto-oncogene mRNA as a cellular AUF1 target. Levels of MYC translation and cell proliferation were proportional to AUF1 abundance but inversely proportional to the abundance of the ARE-binding protein TIAR, a MYC translational suppressor. Both AUF1 and TIAR affected MYC translation via the ARE without affecting mRNA abundance. Altering association of one ARE-binding protein with MYC mRNA in vivo reciprocally affected mRNA association with the other protein. Finally, genetic experiments revealed that AUF1 and TIAR control proliferation by a MYC-dependent pathway. Together, these observations suggest a novel regulatory mechanism where tuning the ratios of AUF1 and TIAR bound to MYC mRNA permits dynamic control of MYC translation and cell proliferation.
authors.affiliation: Department of Molecular Genetics, Microbiology, and Immunology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane, Piscataway, New Jersey 08854, USA.
authors.forename: Baisong
authors.initials: B
authors.lastname: Liao
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.forename: Gary
authors.initials: G
authors.lastname: Brewer
mesh_terms: D000704:Analysis of Variance; D001667:Binding, Competitive / Q000235:genetics*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016259:Genes, myc / Q000235:genetics*; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D011132:Polyribosomes / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C076751:TIAL1 protein, human