scholarly journals MicroRNA-mediated repression of nonsense mRNAs

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Ya Zhao ◽  
Jimin Lin ◽  
Beiying Xu ◽  
Sida Hu ◽  
Xue Zhang ◽  
...  
Keyword(s):  
Surveillance System ◽  
Untranslated Region ◽  
Premature Termination Codon ◽  
Exon Junction Complex ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Coding Region ◽  
Exon Junction ◽  
Naturally Occurring ◽  
Nonsense Mediated Mrna Decay

Numerous studies have established important roles for microRNAs (miRNAs) in regulating gene expression. Here, we report that miRNAs also serve as a surveillance system to repress the expression of nonsense mRNAs that may produce harmful truncated proteins. Upon recognition of the premature termination codon by the translating ribosome, the downstream portion of the coding region of an mRNA is redefined as part of the 3′ untranslated region; as a result, the miRNA-responsive elements embedded in this region can be detected by miRNAs, triggering accelerated mRNA deadenylation and translational inhibition. We demonstrate that naturally occurring cancer-causing APC (adenomatous polyposis coli) nonsense mutants which escape nonsense-mediated mRNA decay (NMD) are repressed by miRNA-mediated surveillance. In addition, we show that miRNA-mediated surveillance and exon–exon junction complex-mediated NMD are not mutually exclusive and act additively to enhance the repressive activity. Therefore, we have uncovered a new role for miRNAs in repressing nonsense mutant mRNAs.

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 Mammalian UPF3A and UPF3B activate NMD independently of their EJC binding

2021 ◽  
Author(s):  
Zhongxia Yi ◽  
René M Arvola ◽  
Sean Myers ◽  
Corinne N Dilsavor ◽  
Rabab Abu Alhasan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Active Role ◽  
Exon Junction Complex ◽  
Human Cell Lines ◽  
Wild Type ◽  
Human Colorectal Cancer ◽  
Independent Manner ◽  
Exon Junction ◽  
Nonsense Mediated Mrna Decay ◽  
Hct116 Cells

Nonsense-mediated mRNA decay (NMD) is governed by the three conserved factors - UPF1, UPF2 and UPF3. While all three are required for NMD in yeast, UPF3B is dispensable for NMD in mammals, with its paralog UPF3A suggested to only weakly activate or even repress NMD due to its weaker binding to the exon junction complex (EJC). Here we characterize the UPF3B-dependent and -independent NMD in human cell lines knocked-out of one or both UPF3 paralogs. We show that in human colorectal cancer HCT116 cells, EJC-mediated NMD can operate in UPF3B-dependent and -independent manner. While UPF3A is almost completely dispensable for NMD in wild-type cells, it strongly activates EJC-mediated NMD in cells lacking UPF3B. Surprisingly, this major NMD branch can operate in UPF3-independent manner questioning the idea that UPF3 is needed to bridge UPF proteins to the EJC during NMD. Complementation studies in UPF3 knockout cells further show that EJC-binding domain of UPF3 paralogs is not essential for NMD. Instead, the conserved mid domain of UPF3B, previously shown to engage with ribosome release factors, is required for its full NMD activity. Altogether, UPF3 plays a more active role in NMD than simply being a bridge between the EJC and the UPF complex.

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 A Day in the Life of the Exon Junction Complex

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 866 ◽  
Author(s):  
Lena P. Schlautmann ◽  
Niels H. Gehring
Keyword(s):  
Mrna Export ◽  
Mrna Splicing ◽  
Exon Junction Complex ◽  
Chronological Order ◽  
Exon Junction ◽  
Messenger Ribonucleoprotein ◽  
Associated Proteins ◽  
Core Components ◽  
Nonsense Mediated Mrna Decay ◽  
Exon Junctions

The exon junction complex (EJC) is an abundant messenger ribonucleoprotein (mRNP) component that is assembled during splicing and binds to mRNAs upstream of exon-exon junctions. EJCs accompany the mRNA during its entire life in the nucleus and the cytoplasm and communicate the information about the splicing process and the position of introns. Specifically, the EJC’s core components and its associated proteins regulate different steps of gene expression, including pre-mRNA splicing, mRNA export, translation, and nonsense-mediated mRNA decay (NMD). This review summarizes the most important functions and main protagonists in the life of the EJC. It also provides an overview of the latest findings on the assembly, composition and molecular activities of the EJC and presents them in the chronological order, in which they play a role in the EJC’s life cycle.

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 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.

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