scholarly journals Harnessing short poly(A)-binding protein-interacting peptides for the suppression of nonsense-mediated mRNA decay

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Tobias Fatscher ◽  
Niels H. Gehring
Keyword(s):  
Mrna Decay ◽  
Binding Protein ◽  
Nonsense Mediated Mrna Decay

scholarly journals Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Zhiyun Ge ◽  
Bao Lin Quek ◽  
Karen L Beemon ◽  
J Robert Hogg
Keyword(s):  
Gene Expression ◽  
Mrna Decay ◽  
Gene Expression Regulation ◽  
Stop Codon ◽  
Binding Protein ◽  
Polypyrimidine Tract ◽  
Polypyrimidine Tract Binding ◽  
Stop Codons ◽  
Polypyrimidine Tract Binding Protein ◽  
Nonsense Mediated Mrna Decay

The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD.

scholarly journals The RNA Binding Protein ELF9 Directly Reduces SUPPRESSOR OF OVEREXPRESSION OF CO1 Transcript Levels in Arabidopsis, Possibly via Nonsense-Mediated mRNA Decay

2009 ◽  
Vol 21 (4) ◽  
pp. 1195-1211 ◽  
Author(s):  
Hae-Ryong Song ◽  
Ju-Dong Song ◽  
Jung-Nam Cho ◽  
Richard M. Amasino ◽  
Bosl Noh ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Transcript Levels ◽  
Nonsense Mediated Mrna Decay

The nuclear cap-binding protein complex is not essential for nonsense-mediated mRNA decay (NMD) in plants.

2008 ◽  
Vol 55 (4) ◽  
pp. 825-828 ◽  
Author(s):  
Agnieszka Dzikiewicz-Krawczyk ◽  
Paulina Piontek ◽  
Zofia Szweykowska-Kulińska ◽  
Artur Jarmołowski
Keyword(s):  
Protein Complex ◽  
Mrna Decay ◽  
Splice Variants ◽  
Binding Protein ◽  
Direct Sequencing ◽  
Premature Termination Codon ◽  
Wild Type ◽  
Mrna Variants ◽  
Nonsense Mediated Mrna Decay ◽  
Alternatively Spliced

In this study we investigated whether in plants, like in mammals, components of the nuclear cap-binding protein complex (CBC) are involved in nonsense-mediated mRNA decay (NMD). We selected several genes producing at least two alternatively spliced mRNA variants: one with a premature termination codon (PTC+) and another without it (PTC-). For each gene the PTC+/PTC- ratio was calculated using RT-PCR and direct sequencing in four Arabidopsis thaliana lines: wild type, the NMD mutant atupf3-1 and two CBC mutants: cbp20 and abh1. Whereas in the NMD mutant the ratios of PTC+/PTC- splice variants were higher than in wild-type plants, the two CBC mutants investigated showed no change in the PTC+/PTC- ratios. Our results suggest that neither CBP20 nor CBP80 is involved in NMD in A. thaliana.

scholarly journals UPF1 Association with the Cap-Binding Protein, CBP80, Promotes Nonsense-Mediated mRNA Decay at Two Distinct Steps

2010 ◽  
Vol 39 (3) ◽  
pp. 396-409 ◽  
Author(s):  
Jungwook Hwang ◽  
Hanae Sato ◽  
Yalan Tang ◽  
Daiki Matsuda ◽  
Lynne E. Maquat
Keyword(s):  
Mrna Decay ◽  
Binding Protein ◽  
Nonsense Mediated Mrna Decay

scholarly journals Complexes between the nonsense-mediated mRNA decay pathway factor human upf1 (up-frameshift protein 1) and essential nonsense-mediated mRNA decay factors in HeLa cells

2003 ◽  
Vol 373 (3) ◽  
pp. 775-783 ◽  
Author(s):  
Thomas SCHELL ◽  
Thomas KÖCHER ◽  
Matthias WILM ◽  
Bertrand SERAPHIN ◽  
Andreas E. KULOZIK ◽  
...  
Keyword(s):  
Cell Line ◽  
Mrna Decay ◽  
Translation Termination ◽  
Binding Protein ◽  
Size Exclusion ◽  
Exon Junction Complex ◽  
Affinity Tag ◽  
Exclusion Chromatography ◽  
Associated Proteins ◽  
Nonsense Mediated Mrna Decay

mRNAs harbouring premature translation-termination codons are usually degraded by the nonsense-mediated mRNA decay (NMD) pathway. Human up-frameshift protein 1 (Hupf1) is an NMD factor that is conserved between yeast and mammals. To isolate cellular complexes that are formed with Hupf1 and to explore the role of cellular proteins in NMD, we generated a HeLa cell line that stably expresses Hupf1 bearing a double-affinity tag (termed Hupf1-2tag). Hupf1-2tag is localized in the cytoplasm similar to the endogenous Hupf1 protein, and the Hupf1-2tag cell line is fully NMD-competent. Using affinity chromatography, Hupf1-2tag-associated proteins were isolated. MS and immunoblotting identified the NMD factors Hupf2 and Hupf3a/b as interaction partners of Hupf1. Size-exclusion chromatography indicates that the NMD factors Hupf1, Hupf2 and the large isoform of Hupf3a might exist in a stable, high-molecular-mass complex of approx. 1.3 MDa. Interestingly, the poly(A)-binding protein was also identified by MS to be associated specifically with Hupf1-2tag. In contrast with the interaction with Hupf2 and Hupf3a/b, the association of poly(A)-binding protein with Hupf1 is highly sensitive to treatment of the isolated complexes with RNase. Components of the exon–exon junction complex or the translational eukaryotic release factor (eRF) 3 were not identified in complexes associated with Hupf1-2tag. We discuss these findings in the context of current models of NMD.

scholarly journals The GTP-binding Release Factor eRF3 as a Key Mediator Coupling Translation Termination to mRNA Decay

2004 ◽  
Vol 279 (44) ◽  
pp. 45693-45700 ◽  
Author(s):  
Tetsuo Kobayashi ◽  
Yuji Funakoshi ◽  
Shin-ichi Hoshino ◽  
Toshiaki Katada
Keyword(s):  
Mrna Decay ◽  
Translation Termination ◽  
Binding Protein ◽  
Binding Activity ◽  
Release Factor ◽  
Guanine Nucleotide Binding Protein ◽  
Eukaryotic Translation ◽  
Gtp Binding ◽  
Nonsense Mediated Mrna Decay ◽  
Guanine Nucleotide Binding

GTP is essential for eukaryotic translation termination, where the release factor 3 (eRF3) complexed with eRF1 is involved as the guanine nucleotide-binding protein. In addition, eRF3 regulates the termination-coupled events, eRF3 interacts with poly(A)-binding protein (Pab1) and the surveillance factor Upf1 to mediate normal and nonsense-mediated mRNA decay. However, the roles of GTP binding to eRF3 in these processes remain largely unknown. Here, we showed in yeast that GTP is essentially required for the association of eRF3 with eRF1, but not with Pab1 and Upf1. A mutation in the GTP-binding motifs of eRF3 impairs the eRF1-binding ability without altering the Pab1- or Upf1-binding activity. Interestingly, the mutation causes not only a defect in translation termination but also delay of normal and nonsense-mediated mRNA decay, suggesting that GTP/eRF3-dependent termination exerts its influence on the subsequent mRNA degradation. The termination reaction itself is not sufficient, but eRF3 is essential for triggering mRNA decay. Thus, eRF3 is a key mediator that transduces termination signal to mRNA decay.

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