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 Nonsense-Mediated mRNA Decay: Pathologies and the Potential for Novel Therapeutics

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 765 ◽  
Author(s):  
Kamila Pawlicka ◽  
Umesh Kalathiya ◽  
Javier Alfaro
Keyword(s):  
Messenger Rna ◽  
Mrna Decay ◽  
Tumour Progression ◽  
Transcript Abundance ◽  
Tumour Suppressor Genes ◽  
Nonsense Mediated Mrna Decay ◽  
The Many ◽  
Cycle Regulation ◽  
Fine Tune

Nonsense-mediated messenger RNA (mRNA) decay (NMD) is a surveillance pathway used by cells to control the quality mRNAs and to fine-tune transcript abundance. NMD plays an important role in cell cycle regulation, cell viability, DNA damage response, while also serving as a barrier to virus infection. Disturbance of this control mechanism caused by genetic mutations or dys-regulation of the NMD pathway can lead to pathologies, including neurological disorders, immune diseases and cancers. The role of NMD in cancer development is complex, acting as both a promoter and a barrier to tumour progression. Cancer cells can exploit NMD for the downregulation of key tumour suppressor genes, or tumours adjust NMD activity to adapt to an aggressive immune microenvironment. The latter case might provide an avenue for therapeutic intervention as NMD inhibition has been shown to lead to the production of neoantigens that stimulate an immune system attack on tumours. For this reason, understanding the biology and co-option pathways of NMD is important for the development of novel therapeutic agents. Inhibitors, whose design can make use of the many structures available for NMD study, will play a crucial role in characterizing and providing diverse therapeutic options for this pathway in cancer and other diseases.

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 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 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 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
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