Nonsense-mediated translational repression involves exon junction complex downstream of premature translation termination codon.
Human transforming growth factor-beta receptor type 2 (TGFbetaR2) 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 TGFbetaR2 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.
Lee
Hyung Chul
HC
School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Oh
Nara
N
Cho
Hana
H
Choe
Junho
J
Kim
Yoon Ki
YK
D017398:Alternative Splicing; D015153:Blotting, Western; D018389:Codon, Nonsense / Q000235:genetics*; D039601:Eukaryotic Initiation Factor-4A / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D020365:RNA Helicases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D018389:Codon, Nonsense; C406243:RBM8A protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D015534:Trans-Activators; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D039601:Eukaryotic Initiation Factor-4A; D020365:RNA Helicases; C101828:UPF1 protein, human