Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay.

By Isao Kashima, A. Yamashita, Natsuko Izumi, N. Kataoka, R. Morishita, S. Hoshino, M. Ohno, G. Dreyfuss, S. Ohno. Genes & Development, 2006

649 citations recorded by the source corpus.

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that degrades mRNA containing premature termination codons (PTCs). In mammalian cells, recognition of PTCs requires translation and depends on the presence on the mRNA with the splicing-dependent exon junction complex (EJC). While it is known that a key event in the triggering of NMD is phosphorylation of the trans-acting factor, Upf1, by SMG-1, the relationship between Upf1 phosphorylation and PTC recognition remains undetermined. Here we show that SMG-1 binds to the mRNA-associated components of the EJC, Upf2, Upf3b, eIF4A3, Magoh, and Y14. Further, we describe a novel complex that contains the NMD factors SMG-1 and Upf1, and the translation termination release factors eRF1 and eRF3 (SURF). Importantly, an association between SURF and the EJC is required for SMG-1-mediated Upf1 phosphorylation and NMD. Thus, the SMG-1-mediated phosphorylation of Upf1 occurs on the association of SURF with EJC, which provides the link between the EJC and recognition of PTCs and triggers NMD.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/06cd978d4b3a764e8e7200c5199aa246f741b420

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In Molecular Biology

1. R. Parker
2. Ujwal Sheth
3. O. Isken
4. L. Maquat
5. R. Pillai
6. Elisa Izaurralde
7. Paul Anderson
8. N. Kedersha

Citations in the corpus

• Regulation of cytoplasmic mRNA decay (2012, background): “SMG5–SMG7 and/or SMG6 also promote dephosphorylation of UPF1 by protein phosphatase 2A (PP2A), which enables UPF1 recyclin”
• Pre-mRNA processing reaches back to transcription and ahead to translation. (2009, neutral): “Contact between the SURF complex and Upf2 bound to a downstream EJC triggers phosphorylation of Upf1 by SMG1 (Kashima et al., 2006).”
• Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. (2007, background): “…may increase the efficiency of translation termination by recruiting eRF3, with which it interacts directly (Uchida et al. 2002; Amrani et al. 2004; Kashima et al. 2006), since tethering eRF3 downstream from a PTC also abolishes NMD, although not as effectively as tethering Pab1 of PABC1 (Amrani…”
• P bodies and the control of mRNA translation and degradation. (2007, background): “In this process Upf1p recruits components of the general repression/decay complex and thus can target mRNAs to P bodies (Sheth and Parker, 2006), perhaps through direct interactions with Dcp2p (Lykke- Andersen, 2002; He and Jacobson, 1995).”