Structural basis of the PNRC2-mediated link between mRNA surveillance and decapping

Tingfeng Lai, Hana Cho, Zhou Liu, Matthew W. Bowler, Shunfu Piao, Roy Parker, Yoon Ki Kim, Haiwei Song

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Nonsense-mediated mRNA decay (NMD) is an important mRNA surveillance system, and human PNRC2 protein mediates the link between mRNA surveillance and decapping. However, the mechanism by which PNRC2 interacts with the mRNA surveillance machinery and stimulates NMD is unknown. Here, we present the crystal structure of Dcp1a in complex with PNRC2. The proline-rich region of PNRC2 is bound to the EVH1 domain of Dcp1a, while its NR-box mediates the interaction with the hyperphosphorylated Upf1. The mode of PNRC2 interaction with Dcp1a is distinct from those observed in other EVH1/proline-rich ligands interactions. Disruption of the interaction of PNRC2 with Dcp1a abolishes its P-body localization and ability to promote mRNA degradation when tethered to mRNAs. PNRC2 acts in synergy with Dcp1a to stimulate the decapping activity of Dcp2 by bridging the interaction between Dcp1a and Dcp2, suggesting that PNRC2 is a decapping coactivator in addition to its adaptor role in NMD.

Original languageEnglish
Pages (from-to)2025-2037
Number of pages13
JournalStructure
Volume20
Issue number12
DOIs
Publication statusPublished - 2012 Dec 5

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Nonsense Mediated mRNA Decay
Messenger RNA
Proline
RNA Stability
Ligands

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Lai, T., Cho, H., Liu, Z., Bowler, M. W., Piao, S., Parker, R., ... Song, H. (2012). Structural basis of the PNRC2-mediated link between mRNA surveillance and decapping. Structure, 20(12), 2025-2037. https://doi.org/10.1016/j.str.2012.09.009

Structural basis of the PNRC2-mediated link between mRNA surveillance and decapping. / Lai, Tingfeng; Cho, Hana; Liu, Zhou; Bowler, Matthew W.; Piao, Shunfu; Parker, Roy; Kim, Yoon Ki; Song, Haiwei.

In: Structure, Vol. 20, No. 12, 05.12.2012, p. 2025-2037.

Research output: Contribution to journalArticle

Lai, T, Cho, H, Liu, Z, Bowler, MW, Piao, S, Parker, R, Kim, YK & Song, H 2012, 'Structural basis of the PNRC2-mediated link between mRNA surveillance and decapping', Structure, vol. 20, no. 12, pp. 2025-2037. https://doi.org/10.1016/j.str.2012.09.009
Lai T, Cho H, Liu Z, Bowler MW, Piao S, Parker R et al. Structural basis of the PNRC2-mediated link between mRNA surveillance and decapping. Structure. 2012 Dec 5;20(12):2025-2037. https://doi.org/10.1016/j.str.2012.09.009
Lai, Tingfeng ; Cho, Hana ; Liu, Zhou ; Bowler, Matthew W. ; Piao, Shunfu ; Parker, Roy ; Kim, Yoon Ki ; Song, Haiwei. / Structural basis of the PNRC2-mediated link between mRNA surveillance and decapping. In: Structure. 2012 ; Vol. 20, No. 12. pp. 2025-2037.
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