Nonsense-mediated translational repression involves exon junction complex downstream of premature translation termination codon

Human transforming growth factor-beta receptor type 2 (TGF beta R2) mRNA harboring a premature translation termination codon (PTC) generated by frameshift mutation is targeted for nonsense-mediated translational repression (NMTR), rather than nonsense-mediated mRNA decay (NMD). Here we show that exon junction complex (EJC) downstream of a PTC plays an inhibitory role in translation of TGF beta R2 mRNA. Translational repression by core EJC components occurs after formation of 80S ribosome complex, which is demonstrated using different types of internal ribosome entry sites (IRESes). Our findings implicate EJCs or core EJC components as negative regulators of translation. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.