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

Stable Identifier
R-HSA-975956
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
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
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
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
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