Decay of mRNA in SMG6:SMG5:SMG7:mRNA complex

Stable Identifier
R-HSA-927830
Type
Reaction [omitted]
Species
Homo sapiens
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SMG6 endonucleolytically cleaves an mRNA it is believed that the resulting fragments are degraded by exonucleases, possibly XRN1, a 5'-to-3' nuclease, and the exosome complex, a 3'-to-5' nuclease (Huntzinger et al. 2008, Eberle et al. 2009). Inhibition of XRN1 is observed to cause accumulation of SMG6-cleaved intermediates therefore XRN1 is postulated to act downstream of SMG6 (Huntzinger et al. 2008).
In general, during Nonsense-Mediated Decay mRNAs are observed to be deadenlyated (implicating the PAN2 complex, PARN complex, and CCR4 complex), decapped (implicating the DCP1:DCP2 complex), and exoribonucleolytically digested (implicating the XRN1 5'-to-3' exonuclease and exosome 3'-to-5' exonuclease) (Lykke-Andersen 2002, Chen et al. 2003, Lejeune et al. 2003, Couttet and Grange 2004, Unterholzner and Izaurralde 2004, Yamashita et al. 2005). UPF1 is observed to associate with the decapping enzymes DCP1a and DCP2, however the specific decay reactions that occur after SMG6, SMG5 and SMG7 have associated with an mRNA are unknown (Lykke-Andersen et al. 2002). Likewise, SMG6 may be present in complexes separate from SMG5 and SMG7 and these complexes may have different routes of decay (reviewed in Nicholson et al. 2010, Muhlemann and Lykke-Andersen 2010).
ATPase activity of UPF1 is necessary for NMD and may reflect ATP-dependent helicase activity that disassembles the mRNA-protein complex (Franks et al. 2010). UPF1 must be dephosphorylated by PP2A for NMD to continue (Ohnishi et al. 2003, Chiu et al. 2003). Presumably the dephosphoryation recycles UPF1 for interaction with other mRNA complexes.

Literature References
PubMed ID Title Journal Year
14636577 Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7

Ohnishi, T, Yamashita, A, Kashima, I, Schell, T, Anders, KR, Grimson, A, Hachiya, T, Hentze, MW, Anderson, P, Ohno, S

Mol Cell 2003
20023408 How and where are nonsense mRNAs degraded in mammalian cells?

Muhlemann, O, Lykke-Andersen, J

RNA Biol 2010
16284618 Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover

Yamashita, A, Chang, TC, Yamashita, Y, Zhu, W, Zhong, Z, Chen, CY, Shyu, AB

Nat Struct Mol Biol 2005
14742663 Premature termination codons enhance mRNA decapping in human cells

Couttet, P, Grange, T

Nucleic Acids Res 2004
15546618 SMG7 acts as a molecular link between mRNA surveillance and mRNA decay

Unterholzner, L, Izaurralde, E

Mol Cell 2004
18974281 SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan

Huntzinger, E, Kashima, I, Fauser, M, Saulière, J, Izaurralde, E

RNA 2008
21145460 Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay

Franks, TM, Singh, G, Lykke-Andersen, J

Cell 2010
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
20930030 SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay

Kashima, I, Jonas, S, Jayachandran, U, Buchwald, G, Conti, E, Lupas, AN, Izaurralde, E

Genes Dev 2010
12417715 Identification of a human decapping complex associated with hUpf proteins in nonsense-mediated decay

Lykke-Andersen, J

Mol Cell Biol 2002
14527413 Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities

Lejeune, F, Li, X, Maquat, LE

Mol Cell 2003
12554878 Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1

Chiu, SY, Serin, G, Ohara, O, Maquat, LE

RNA 2003
12832468 Rapid deadenylation triggered by a nonsense codon precedes decay of the RNA body in a mammalian cytoplasmic nonsense-mediated decay pathway

Chen, CY, Shyu, AB

Mol Cell Biol 2003
19060897 SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells

Eberle, AB, Lykke-Andersen, S, Muhlemann, O, Jensen, TH

Nat Struct Mol Biol 2009
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