Reactome: A Curated Pathway Database

p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A

Stable Identifier
R-HSA-927813
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

SMG6, SMG5 and SMG7 contain 14-3-3 domains which are believed to bind phosphorylated SQ motifs in UPF1 (Chiu et al. 2003, Ohnishi et al. 2003, Unterholzner and Izaurralde 2004, Fukuhara et al. 2005, Durand et al. 2007). SMG7 has been shown to bind UPF1 directly, target UPF1 for dephosphorylation by PP2A, and recruit enzymes that degrade RNA (Ohnishi et al. 2003, Unterholzner and Izaurralde 2004, Fukuhara et al. 2005). UPF3AS (the small isoform of UPF3A) also associates with the complex (Ohnishi et al. 2003). SMG6 is an endoribonuclease that cleaves the mRNA bound by UPF1 and also recruits phosphatase PP2A to dephosphorylate UPF1 (Chiu et al. 2003, Glavan et al. 2006, Eberle et al. 2009). PNRC2 binds both phospo-UPF1 and the decapping enzyme DCP1A, thereby facilitating decapping of the mRNA (Cho et al. 2009, Lai et al. 2012, Cho et al. 2013).
Though immunofluorescence in vivo indicates that SMG5 and SMG7 exist in separate complexes from SMG6 (Unterholzner and Izaurralde 2004) immunoprecipitation shows that SMG6 is present in complexes that also contain SMG5, SMG7, UPF1, UPF2, Y14, Magoh, and PABP (Kashima et al. 2010). SMG5, SMG6, and SMG7 are therefore represented here together in the same RNP complex. It is possible that some complexes contain only SMG6 or SMG5:SMG7 (reviewed in Nicholson et al. 2010, Muhlemann and Lykke-Andersen 2010). Note that "Smg5/7a" in Chiu et al. 2003 actually refers to SMG6.
Phosphorylated UPF1 also inhibits translation initiation by inhibiting conversion of 40S:tRNAmet:mRNA to 80S:tRNAmet:mRNA complexes (Isken et al. 2008)

Literature References
PubMed ID Title Journal Year
12554878 Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1 RNA 2003
20023408 How and where are nonsense mRNAs degraded in mammalian cells? RNA Biol 2010
19150429 Human proline-rich nuclear receptor coregulatory protein 2 mediates an interaction between mRNA surveillance machinery and decapping complex Mol. Cell 2009
17893241 Inhibition of nonsense-mediated mRNA decay (NMD) by a new chemical molecule reveals the dynamic of NMD factors in P-bodies J Cell Biol 2007
14636577 Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7 Mol Cell 2003
23234702 SMG5-PNRC2 is functionally dominant compared with SMG5-SMG7 in mammalian nonsense-mediated mRNA decay Nucleic Acids Res. 2013
20930030 SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay Genes Dev 2010
19060897 SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells Nat Struct Mol Biol 2009
15546618 SMG7 acts as a molecular link between mRNA surveillance and mRNA decay Mol Cell 2004
15721257 SMG7 is a 14-3-3-like adaptor in the nonsense-mediated mRNA decay pathway Mol Cell 2005
23085078 Structural basis of the PNRC2-mediated link between mrna surveillance and decapping Structure 2012
17053788 Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex EMBO J 2006
18423202 Upf1 phosphorylation triggers translational repression during nonsense-mediated mRNA decay Cell 2008
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