Inhibition of nonsense-mediated mRNA decay by the natural product pateamine a through eukaryotic initiation factor 4AIII

Yongjun Dang, Woon Kai Low, Jing Xu, Niels H. Gehring, Harry C Dietz, Daniel Romo, Jun Liu

Research output: Contribution to journalArticle

Abstract

Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A (PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulateNMD.Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.

Original languageEnglish (US)
Pages (from-to)23613-23621
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number35
DOIs
StatePublished - Aug 28 2009

Fingerprint

Nonsense Mediated mRNA Decay
Eukaryotic Initiation Factors
Biological Products
Messenger RNA
Nonsense Codon
Cycloheximide
Phosphorylation
Exons
Proteins
Cells
pateamine A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Inhibition of nonsense-mediated mRNA decay by the natural product pateamine a through eukaryotic initiation factor 4AIII. / Dang, Yongjun; Low, Woon Kai; Xu, Jing; Gehring, Niels H.; Dietz, Harry C; Romo, Daniel; Liu, Jun.

In: Journal of Biological Chemistry, Vol. 284, No. 35, 28.08.2009, p. 23613-23621.

Research output: Contribution to journalArticle

Dang, Yongjun ; Low, Woon Kai ; Xu, Jing ; Gehring, Niels H. ; Dietz, Harry C ; Romo, Daniel ; Liu, Jun. / Inhibition of nonsense-mediated mRNA decay by the natural product pateamine a through eukaryotic initiation factor 4AIII. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 35. pp. 23613-23621.
@article{fc79bfcdbbfa43c9981866fd7e285889,
title = "Inhibition of nonsense-mediated mRNA decay by the natural product pateamine a through eukaryotic initiation factor 4AIII",
abstract = "Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A (PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulateNMD.Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.",
author = "Yongjun Dang and Low, {Woon Kai} and Jing Xu and Gehring, {Niels H.} and Dietz, {Harry C} and Daniel Romo and Jun Liu",
year = "2009",
month = "8",
day = "28",
doi = "10.1074/jbc.M109.009985",
language = "English (US)",
volume = "284",
pages = "23613--23621",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "35",

}

TY - JOUR

T1 - Inhibition of nonsense-mediated mRNA decay by the natural product pateamine a through eukaryotic initiation factor 4AIII

AU - Dang, Yongjun

AU - Low, Woon Kai

AU - Xu, Jing

AU - Gehring, Niels H.

AU - Dietz, Harry C

AU - Romo, Daniel

AU - Liu, Jun

PY - 2009/8/28

Y1 - 2009/8/28

N2 - Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A (PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulateNMD.Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.

AB - Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A (PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulateNMD.Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.

UR - http://www.scopus.com/inward/record.url?scp=69949118279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69949118279&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109.009985

DO - 10.1074/jbc.M109.009985

M3 - Article

VL - 284

SP - 23613

EP - 23621

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 35

ER -