Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation |
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Authors: | Liao Baisong Hu Yan Brewer Gary |
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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. |
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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. |
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