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Proc Natl Acad Sci U S A
2004 Mar 23;10112:4118-23. doi: 10.1073/pnas.0400933101.
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A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay.
Ferraiuolo MA
,
Lee CS
,
Ler LW
,
Hsu JL
,
Costa-Mattioli M
,
Luo MJ
,
Reed R
,
Sonenberg N
.
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In eukaryotes, a surveillance mechanism known as nonsense-mediated decay (NMD) degrades the mRNA when a premature-termination codon (PTC) is present. NMD requires translation to read the frame of the mRNA and detect the PTC. During pre-mRNA splicing, the exon-exon junction complex (EJC) is recruited to a region 20-24 nt upstream of the exon junction on the mature mRNA. The presence of a PTC upstream from the EJC elicits NMD. Eukaryotic initiation factor 4A (eIF4A) III is a nuclear protein that interacts physically or functionally with translation initiation factors eIF4G and eIF4B, respectively, and shares strikingly high identity with the initiation factors eIF4AI/II. Here we show that siRNA against eIF4AIII, but not against eIF4AI/II, inhibits NMD. Moreover, eIF4AIII, but not eIF4AI, is specifically recruited to the EJC during splicing. The observations that eIF4AIII is loaded onto the mRNA during splicing in the nucleus, has properties related to a translation initiation factor, and functions in NMD raises the possibility that eIF4AIII substitutes for eIF4AI/II during NMD.
Belgrader,
Evidence to implicate translation by ribosomes in the mechanism by which nonsense codons reduce the nuclear level of human triosephosphate isomerase mRNA.
1993, Pubmed
Belgrader,
Evidence to implicate translation by ribosomes in the mechanism by which nonsense codons reduce the nuclear level of human triosephosphate isomerase mRNA.
1993,
Pubmed
Bohnsack,
Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm.
2002,
Pubmed
Brocke,
The human intronless melanocortin 4-receptor gene is NMD insensitive.
2002,
Pubmed
Carter,
A splicing-dependent regulatory mechanism that detects translation signals.
1996,
Pubmed
Carter,
A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro.
1995,
Pubmed
Chan,
eIF4A3 is a novel component of the exon junction complex.
2004,
Pubmed
Conroy,
Characterization of the 46,000-dalton subunit of eIF-4F.
1990,
Pubmed
Daniels-McQueen,
Unusual requirements for optimum translation of polio viral RNA in vitro.
1983,
Pubmed
Dostie,
A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5' cap-binding protein, eIF4E.
2000,
Pubmed
Dreyfuss,
Messenger-RNA-binding proteins and the messages they carry.
2002,
Pubmed
Fan,
HNS, a nuclear-cytoplasmic shuttling sequence in HuR.
1998,
Pubmed
,
Xenbase
Frischmeyer,
Nonsense-mediated mRNA decay in health and disease.
1999,
Pubmed
Gingras,
eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation.
1999,
Pubmed
Hentze,
A perfect message: RNA surveillance and nonsense-mediated decay.
1999,
Pubmed
Holzmann,
A human common nuclear matrix protein homologous to eukaryotic translation initiation factor 4A.
2000,
Pubmed
Iborra,
Coupled transcription and translation within nuclei of mammalian cells.
2001,
Pubmed
Ishigaki,
Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20.
2001,
Pubmed
Izaurralde,
Nuclear export of messenger RNA.
2002,
Pubmed
Izaurralde,
A novel family of nuclear transport receptors mediates the export of messenger RNA to the cytoplasm.
2002,
Pubmed
Jurica,
Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.
2002,
Pubmed
Jurica,
Pre-mRNA splicing: awash in a sea of proteins.
2003,
Pubmed
Kataoka,
Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm.
2000,
Pubmed
,
Xenbase
Le Hir,
The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions.
2000,
Pubmed
,
Xenbase
Le Hir,
The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay.
2001,
Pubmed
,
Xenbase
Lejbkowicz,
A fraction of the mRNA 5' cap-binding protein, eukaryotic initiation factor 4E, localizes to the nucleus.
1992,
Pubmed
Li,
T cell receptor (TCR) mini-gene mRNA expression regulated by nonsense codons: a nuclear-associated translation-like mechanism.
1997,
Pubmed
Li,
Eukaryotic translation initiation factor 4AIII (eIF4AIII) is functionally distinct from eIF4AI and eIF4AII.
1999,
Pubmed
,
Xenbase
Li,
Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo.
2001,
Pubmed
Luo,
Splicing is required for rapid and efficient mRNA export in metazoans.
1999,
Pubmed
,
Xenbase
Luo,
Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly.
2001,
Pubmed
,
Xenbase
Maquat,
Mammalian heat shock p70 and histone H4 transcripts, which derive from naturally intronless genes, are immune to nonsense-mediated decay.
2001,
Pubmed
Maquat,
Nonsense-mediated mRNA decay.
2002,
Pubmed
Mendell,
Novel Upf2p orthologues suggest a functional link between translation initiation and nonsense surveillance complexes.
2000,
Pubmed
Mendell,
Separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts.
2002,
Pubmed
Mühlemann,
Precursor RNAs harboring nonsense codons accumulate near the site of transcription.
2001,
Pubmed
Nagy,
A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance.
1998,
Pubmed
Nathanson,
Nuclear protein synthesis: a re-evaluation.
2003,
Pubmed
Neu-Yilik,
Splicing and 3' end formation in the definition of nonsense-mediated decay-competent human beta-globin mRNPs.
2001,
Pubmed
Palacios,
An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay.
2004,
Pubmed
Piñol-Roma,
Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm.
1992,
Pubmed
,
Xenbase
Rappsilber,
Large-scale proteomic analysis of the human spliceosome.
2002,
Pubmed
Reed,
A new view of mRNA export: separating the wheat from the chaff.
2001,
Pubmed
Reed,
A conserved mRNA export machinery coupled to pre-mRNA splicing.
2002,
Pubmed
Svitkin,
The requirement for eukaryotic initiation factor 4A (elF4A) in translation is in direct proportion to the degree of mRNA 5' secondary structure.
2001,
Pubmed
Wagner,
mRNA surveillance: the perfect persist.
2002,
Pubmed
Wang,
A quality control pathway that down-regulates aberrant T-cell receptor (TCR) transcripts by a mechanism requiring UPF2 and translation.
2002,
Pubmed
Wang,
Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay.
2002,
Pubmed
Weinstein,
Epidermal induction and inhibition of neural fate by translation initiation factor 4AIII.
1997,
Pubmed
,
Xenbase
Zhang,
Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm.
1998,
Pubmed
Zhang,
At least one intron is required for the nonsense-mediated decay of triosephosphate isomerase mRNA: a possible link between nuclear splicing and cytoplasmic translation.
1998,
Pubmed
Zhou,
The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans.
2000,
Pubmed
Zhou,
Comprehensive proteomic analysis of the human spliceosome.
2002,
Pubmed
