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

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

Stable Identifier

R-HSA-927789

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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

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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 Eberle, AB, Stalder, L, Mathys, H, Orozco, RZ, Muhlemann, O	PLoS Biol	2008
21029861	Upf1 senses 3'UTR length to potentiate mRNA decay Hogg, JR, Goff, SP	Cell	2010
18230761	Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay Silva, AL, Ribeiro, P, Inácio, A, Liebhaber, SA, Romão, L	RNA	2008
18447585	A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay Singh, G, Rebbapragada, I, Lykke-Andersen, J	PLoS Biol	2008
16622410	EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3' UTR length Buhler, M, Steiner, S, Mohn, F, 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, Hentze, MW, Kulozik, AE	EMBO J	2008