SMG-8 and SMG-9, two novel subunits of the SMG-1 complex, regulate remodeling of the mRNA surveillance complex during nonsense-mediated mRNA decay.
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades mRNAs containing premature translation termination codons (PTCs). SMG-1 and Upf1 transiently form a surveillance complex termed "SURF" that includes eRF1 and eRF3 on post-spliced mRNAs during recognition of PTC. If an exon junction complex (EJC) exists downstream from the SURF complex, SMG-1 phosphorylates Upf1, the step that is a rate-limiting for NMD. We provide evidence of an association between the SURF complex and the ribosome in association with mRNPs, and we suggest that the SURF complex functions as a translation termination complex during NMD. We identified SMG-8 and SMG-9 as novel subunits of the SMG-1 complex. SMG-8 and SMG-9 suppress SMG-1 kinase activity in the isolated SMG-1 complex and are involved in NMD in both mammals and nematodes. SMG-8 recruits SMG-1 to the mRNA surveillance complex, and inactivation of SMG-8 induces accumulation of a ribosome:Upf1:eRF1:eRF3:EJC complex on mRNP, which physically bridges the ribosome and EJC through eRF1, eRF3, and Upf1. These results not only reveal the regulatory mechanism of SMG-1 kinase but also reveal the sequential remodeling of the ribosome:SURF complex to the predicted DECID (DECay InDucing) complex, a ribosome:SURF:EJC complex, as a mechanism of in vivo PTC discrimination.
Department of Molecular Biology, Yokohama City University School of Medicine, Yokohama, Japan. yamasita@yokohama-cu.ac.jp
Akio
A
Yamashita
Natsuko
N
Izumi
Isao
I
Kashima
Tetsuo
T
Ohnishi
Bonnie
B
Saari
Yukiko
Y
Katsuhata
Reiko
R
Muramatsu
Tomoko
T
Morita
Akihiro
A
Iwamatsu
Takahisa
T
Hachiya
Rie
R
Kurata
Hisashi
H
Hirano
Philip
P
Anderson
Shigeo
S
Ohno
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D018389:Codon, Nonsense / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits / Q000378:metabolism*; D020871:RNA Stability / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018389:Codon, Nonsense; D005978:Glutathione; D009097:Multienzyme Complexes; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; C529051:4-methoxy-1-tyrosyl-gamma-glutamyl-cysteinyl-glycine; C490966:SMG-1 protein, C elegans; C514704:SMG1 protein, human