scholarly journals The Hierarchy of Exon-Junction Complex Assembly by the Spliceosome Explains Key Features of Mammalian Nonsense-Mediated mRNA Decay

PLoS Biology ◽  
2009 ◽  
Vol 7 (5) ◽  
pp. e1000120 ◽  
Author(s):  
Niels H. Gehring ◽  
Styliani Lamprinaki ◽  
Matthias W. Hentze ◽  
Andreas E. Kulozik
Keyword(s):  
Mrna Decay ◽  
Exon Junction Complex ◽  
Complex Assembly ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay ◽  
Key Features

scholarly journals Exon-Junction Complex Components Specify Distinct Routes of Nonsense-Mediated mRNA Decay with Differential Cofactor Requirements

2005 ◽  
Vol 20 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Niels H. Gehring ◽  
Joachim B. Kunz ◽  
Gabriele Neu-Yilik ◽  
Stephen Breit ◽  
Marcelo H. Viegas ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Exon Junction Complex ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay ◽  
Complex Components

scholarly journals The Exon Junction Complex Undergoes a Compositional Switch that Alters mRNP Structure and Nonsense-Mediated mRNA Decay Activity

Cell Reports ◽  
2018 ◽  
Vol 25 (9) ◽  
pp. 2431-2446.e7 ◽  
Author(s):  
Justin W. Mabin ◽  
Lauren A. Woodward ◽  
Robert D. Patton ◽  
Zhongxia Yi ◽  
Mengxuan Jia ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Exon Junction Complex ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay

scholarly journals SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay

2010 ◽  
Vol 24 (21) ◽  
pp. 2440-2450 ◽  
Author(s):  
I. Kashima ◽  
S. Jonas ◽  
U. Jayachandran ◽  
G. Buchwald ◽  
E. Conti ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Exon Junction Complex ◽  
Binding Motifs ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay

scholarly journals A Haploid Genetic Screening Method for Proteins Influencing Mammalian Nonsense-Mediated mRNA Decay Activity

2018 ◽  
Author(s):  
Maximilian W. Popp ◽  
Lynne E. Maquat
Keyword(s):  
Genetic Screening ◽  
Mammalian Cells ◽  
Mrna Decay ◽  
Fluorescent Proteins ◽  
Screening Method ◽  
Transcript Abundance ◽  
Exon Junction Complex ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay

AbstractDespite a long appreciation for the role of nonsense-mediated mRNA decay (NMD) in the destruction of faulty, disease-causing mRNAs, as well as its role in the maintenance of normal, endogenous transcript abundance, systematic unbiased methods for uncovering modifiers of NMD activity in mammalian cells remain scant. Here we present and validate a haploid genetic screening method for identifying proteins and processes that stimulate NMD activity involving a 3′-untranslated region exon-junction complex. This reporterbased screening method can be adapted for interrogating other pathways whose output can be measured by the intracellular production of fluorescent proteins.

scholarly journals The Exon Junction Complex Undergoes a Compositional Switch that Alters mRNP Structure and Nonsense-Mediated mRNA Decay Activity

2018 ◽  
Author(s):  
Justin W. Mabin ◽  
Lauren A. Woodward ◽  
Robert Patton ◽  
Zhongxia Yi ◽  
Mengxuan Jia ◽  
...  
Keyword(s):  
Mrna Decay ◽  
Exon Junction Complex ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay

scholarly journals Polysome fractionation analysis reveals features important for human nonsense-mediated mRNA decay

2020 ◽  
Author(s):  
James P. B. Lloyd ◽  
Courtney E. French ◽  
Steven E. Brenner
Keyword(s):  
Mrna Decay ◽  
Premature Termination ◽  
Stop Codon ◽  
Upstream Open Reading Frame ◽  
Exon Junction Complex ◽  
Alternative Mechanism ◽  
Powerful Predictor ◽  
Exon Junction ◽  
Fractionation Analysis ◽  
Nonsense Mediated Mrna Decay

AbstractNonsense-mediated mRNA decay (NMD) is a translation-dependent mRNA surveillance pathway that eliminates transcripts with premature termination codons. Several studies have tried defined the features governing which transcripts are targeted to NMD. However, these approaches often rely on inhibiting core NMD factors, which often have roles in non-NMD processes within the cell. Based on reports that NMD-targeted transcripts are often bound by a single ribosome, we analyzed RNA-Seq data from a polysome fractionation experiment (TrlP-Seq) to characterize the features of NMD-targeted transcripts in human cells. This approach alleviates the need to inhibit the NMD pathway. We found that the exon junction complex (EJC) model, wherein an exon-exon junction located ≥50 nucleotides downstream of a stop codon is predicted to elicit NMD, was a powerful predictor of transcripts with high abundance in the monosome fraction (bound by a single ribosome). This was also true for the presence of an upstream open reading frame. In contrast, as 3’ UTR lengths increase, the proportion of transcripts that are most abundant in the monosome fraction does not increase. This suggests that either longer 3’ UTRs do not consistently act as potent triggers of NMD or that the degradation of these transcripts is mechanistically different to other NMD-targeted transcripts. Of the ribosome-associated transcripts annotated as “non-coding”, we find that a majority are bound by a single ribosome. Many of these transcripts increase in response to NMD inhibition, including the oncogenic SHNG15, suggesting many might be NMD targets. Finally, we found that retained intron transcripts without a premature termination codon are over-represented in the monosome fraction, suggesting an alternative mechanism is responsible for the low level of translation of these transcripts. In summary, our analysis finds that the EJC model is a powerful predictor of NMD-targeted transcripts, while the presence of a long 3’ UTR is not.

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