Cap Binding Complex (CBC) mRNA Cleaved by SMG6 PP2A (Aalpha:B55alpha:Calpha) Decay of mRNA in SMG6:SMG5:SMG7:mRNA Complex Authored: May, B, 2010-08-06 Edited: May, B, 2010-08-06 Pubmed12417715 Pubmed12554878 Pubmed12832468 Pubmed14527413 Pubmed14636577 Pubmed14742663 Pubmed15546618 Pubmed16284618 Pubmed18974281 Pubmed19060897 Pubmed19859661 Pubmed20023408 Pubmed20930030 Pubmed21145460 Reactome Database ID Release 43927830 Reactome, http://www.reactome.org ReactomeREACT_75794 Reviewed: Neu-Yilik, G, 2011-05-19 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).<br>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).<br>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.