Formation of UPF1:eRF3 complex on mRNA with a premature termination codon and no Exon Junction Complex

Stable Identifier
Reaction [binding]
Homo sapiens
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Nonsense-mediated decay of an mRNA can be triggered even if the termination codon does not precede an exon junction (Buhler et al. 2006, Eberle et al. 2008, Silva et al. 2008, Singh et al. 2008, Ivanov et al. 2008). UPF1 and PABP seem to modulate the efficiency of translation termination and PABP in the proximity of a termination codon prevents NMD likely by outcompeting UPF1 for interaction with eRF3 (Singh et al. 2008, Ivanov et al. 2008, Silva et al. 2008). Factors in the competition may be the length and secondary structure of the 3' UTR (Buhler et al. 2006, Eberle et al. 2008). UPF1 preferentially binds some but not all longer UTRs (Hogg and Goff 2010).
Interaction of eRF3 with PABP stimulates ribosome dissociation and initiation of a new round of translation on the mRNA. Interaction of eRF3 with UPF1 appears to promote nonsense-mediated decay. It is possible but not yet demonstrated that all components of the SURF complex (SMG1, UPF1, eRF1, eRF3) are assembled on an mRNA without an exon junction complex and that UPF1 is phosphorylated by SMG1.

Literature References
PubMed ID Title Journal Year
18447580 Posttranscriptional gene regulation by spatial rearrangement of the 3' untranslated region

Stalder, L, Eberle, AB, Mathys, H, Orozco, RZ, Muhlemann, O

PLoS Biol 2008
21029861 Upf1 senses 3'UTR length to potentiate mRNA decay

Goff, SP, Hogg, JR

Cell 2010
18230761 Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay

Liebhaber, SA, Romão, L, Inácio, A, Ribeiro, P, Silva, AL

RNA 2008
18447585 A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay

Rebbapragada, I, Singh, G, Lykke-Andersen, J

PLoS Biol 2008
16622410 EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3' UTR length

Steiner, S, Mohn, F, Buhler, M, Paillusson, A, Muhlemann, O

Nat Struct Mol Biol 2006
18256688 Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways

Ivanov, PV, Gehring, NH, Kunz, JB, Kulozik, AE, Hentze, MW

EMBO J 2008
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