Reactome | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)

Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)

Stable Identifier

R-HSA-975956

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)

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Nonsense-mediated decay has been observed with mRNAs that do not have an exon junction complex (EJC) downstream of the termination codon (reviewed in Isken and Maquat 2007, Chang et al. 2007, Behm-Ansmant et al. 2007, Rebbapragada and Lykke-Andersen 2009, Nicholson et al. 2010). In these cases the trigger is unknown but a correlation with the length of the 3' UTR has sometimes been seen. The current model posits a competition between PABP and UPF1 for access to eRF3 at the terminating ribosome (Ivanov et al. 2008, Singh et al. 2008, reviewed in Bhuvanagiri et al. 2010). Abnormally long 3' UTRs may prevent PABP from efficiently interacting with eRF3 and allow UPF1 to bind eRF3 instead. Long UTRs with hairpin loops may bring PABP closer to eRF3 and help evade NMD (Eberle et al. 2008).
The pathway of degradation taken during EJC-independent NMD has not been elucidated. It is thought that phosphorylation of UPF1 by SMG1 and recruitment of SMG6 or SMG5 and SMG7 are involved, as with EJC-enhanced NMD, but this has not yet been shown.

Literature References

PubMed ID	Title	Journal	Year
19859661	Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors Nicholson, P, Yepiskoposyan, H, Metze, S, Zamudio Orozco, R, Kleinschmidt, N, Muhlemann, O	Cell Mol Life Sci	2010
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
17531985	mRNA quality control: an ancient machinery recognizes and degrades mRNAs with nonsense codons Behm-Ansmant, I, Kashima, I, Rehwinkel, J, Saulière, J, Wittkopp, N, Izaurralde, E	FEBS Lett	2007
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
20795950	NMD: RNA biology meets human genetic medicine Bhuvanagiri, M, Schlitter, AM, Hentze, MW, Kulozik, AE	Biochem J	2010
17352659	The nonsense-mediated decay RNA surveillance pathway Chang, YF, Imam, JS, Wilkinson, MF	Annu Rev Biochem	2007
19359157	Execution of nonsense-mediated mRNA decay: what defines a substrate? Rebbapragada, I, Lykke-Andersen, J	Curr Opin Cell Biol	2009
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
17671086	Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function Isken, O, Maquat, LE	Genes Dev	2007