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Julia Contreras, Victoria Begley, Laura Marsella, Eduardo Villalobo
The exon junction complex (EJC) is a key element of the splicing machinery. The EJC core is composed of eIF4A3, MAGO, Y14 and MLN51. Few accessory proteins, such as CWC22 or UPF3, bind transiently to the EJC. The EJC has been implicated in the control of the splicing of long introns. To ascertain whether the EJC controls the splicing of short introns, we used Paramecium tetraurelia as a model organism, since it has thousands of very tiny introns. To elucidate whether EJC affects intron splicing in P. tetraurelia, we searched for EJC protein-coding genes, and silenced those genes coding for eIF4A3, MAGO and CWC22...
April 10, 2018: Gene
Moonil Son, Reed B Wickner
The yeast prion [PSI+] is a self-propagating amyloid of Sup35p with a folded in-register parallel β-sheet architecture. In a genetic screen for antiprion genes, using the yeast knockout collection, UPF1/NAM7 and UPF3 , encoding nonsense-mediated mRNA decay (NMD) factors, were frequently detected. Almost all [PSI+] variants arising in the absence of Upf proteins were eliminated by restored normal levels of these proteins, and [PSI+] arises more frequently in upf mutants. Upf1p, complexed with Upf2p and Upf3p, is a multifunctional protein with helicase, ATP-binding, and RNA-binding activities promoting efficient translation termination and degradation of mRNAs with premature nonsense codons...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mian Xiang, Xian Zhang, Yin Deng, Yangyang Li, Jihua Yu, Jianquan Zhu, Xinhe Huang, Jiayu Zhou, Hai Liao
Pieris rapae, a serious Lepidoptera pest of cultivated crucifers, utilizes midgut enzymes to digest food and detoxify secondary metabolites from host plants. A recombinant trypsin inhibitor (COTI) from nonhost plant, Cassia obtusifolia, significantly decreased activities of trypsin-like proteases in the larval midgut on Pieris rapae and could suppress the growth of larvae. In order to know how COTI took effect, transcriptional profiles of P. rapae midgut in response to COTI was studied. A total of 51,544 unigenes were generated and 45...
January 2018: Archives of Insect Biochemistry and Physiology
Alper Celik, Feng He, Allan Jacobson
Nonsense-mediated mRNA decay (NMD) is generally thought to be a eukaryotic mRNA surveillance pathway tasked with the elimination of transcripts harboring an in-frame premature termination codon (PTC). As presently conceived, NMD acting in this manner minimizes the likelihood that potentially toxic polypeptide fragments would accumulate in the cytoplasm. This notion is to be contrasted to the results of systematic RNA-Seq and microarray analyses of NMD substrates in multiple model systems, two different experimental approaches which have shown that many mRNAs identified as NMD substrates fail to contain a PTC...
December 2017: Current Genetics
Miao Tian, Wentao Yang, Jing Zhang, Huai Dang, Xingyi Lu, Chengjie Fu, Wei Miao
Nonsense-mediated mRNA decay (NMD) is essential for removing premature termination codon-containing transcripts from cells. Studying the NMD pathway in model organisms can help to elucidate the NMD mechanism in humans and improve our understanding of how this biologically important process has evolved. Ciliates are among the earliest branching eukaryotes; their NMD mechanism is poorly understood and may be primordial. We demonstrate that highly conserved Upf proteins (Upf1a, Upf2 and Upf3) are involved in the NMD pathway of the ciliate, Tetrahymena thermophila...
June 20, 2017: Nucleic Acids Research
Zeeshan Nasim, Muhammad Fahim, Ji Hoon Ahn
Eukaryotic cells use nonsense-mediated mRNA decay (NMD) to clear aberrant mRNAs from the cell, thus preventing the accumulation of truncated proteins. In Arabidopsis, two UP-Frameshift (UPF) proteins, UPF1 and UPF3, play a critical role in NMD. Although deficiency of UPF1 and UPF3 leads to various developmental defects, little is known about the mechanism underlying the regulation of flowering time by NMD. Here, we showed that the upf1-5 and upf3-1 mutants had a late-flowering phenotype under long-day conditions and the upf1-5 upf3-1 double mutants had an additive effect in delaying flowering time...
2017: Frontiers in Plant Science
Alper Celik, Richard Baker, Feng He, Allan Jacobson
Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression, yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we reevaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1 , UPF2 , or UPF3 genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several noncoding RNAs...
May 2017: RNA
Lucas D Serdar, DaJuan L Whiteside, Kristian E Baker
Nonsense-mediated mRNA decay (NMD) represents a eukaryotic quality control pathway that recognizes and rapidly degrades transcripts harbouring nonsense mutations to limit accumulation of non-functional and potentially toxic truncated polypeptides. A critical component of the NMD machinery is UPF1, an RNA helicase whose ATPase activity is essential for NMD, but for which the precise function and site of action remain unclear. We provide evidence that ATP hydrolysis by UPF1 is required for efficient translation termination and ribosome release at a premature termination codon...
December 23, 2016: Nature Communications
Karina Vexler, Miryam A Cymerman, Irina Berezin, Adi Fridman, Linoy Golani, Michal Lasnoy, Helen Saul, Orit Shaul
Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA surveillance mechanism that degrades aberrant transcripts and controls the levels of many normal mRNAs. It was shown that balanced expression of the NMD factor UPF3 is essential for the maintenance of proper NMD homeostasis in Arabidopsis. UPF3 expression is controlled by a negative feedback loop that exposes UPF3 transcript to NMD. It was shown that the long 3' untranslated region (3' UTR) of UPF3 exposes its transcript to NMD. Long 3' UTRs that subject their transcripts to NMD were identified in several eukaryotic NMD factors...
2016: Frontiers in Plant Science
Katie Gerhardt
No abstract text is available yet for this article.
June 2016: Biology of Reproduction
Christoph Schweingruber, Paolo Soffientini, Marc-David Ruepp, Angela Bachi, Oliver Mühlemann
Proximity-dependent trans-biotinylation by the Escherichia coli biotin ligase BirA mutant R118G (BirA*) allows stringent streptavidin affinity purification of proximal proteins. This so-called BioID method provides an alternative to the widely used co-immunoprecipitation (co-IP) to identify protein-protein interactions. Here, we used BioID, on its own and combined with co-IP, to identify proteins involved in nonsense-mediated mRNA decay (NMD), a post-transcriptional mRNA turnover pathway that targets mRNAs that fail to terminate translation properly...
2016: PloS One
Peng Cui, Tao Chen, Tao Qin, Feng Ding, Zhenyu Wang, Hao Chen, Liming Xiong
Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in eukaryotes that recognizes and degrades transcripts with premature translation-termination codons. The RNA polymerase II C-terminal domain phosphatase-like protein FIERY2 (FRY2; also known as C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 [CPL1]) plays multiple roles in RNA processing in Arabidopsis thaliana Here, we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the dephosphorylation of eIF4AIII...
March 2016: Plant Cell
Kevin Cilano, Zachary Mazanek, Mahmuda Khan, Sarah Metcalfe, Xiao-Ning Zhang
The exon-exon junction complex (EJC) is a conserved eukaryotic multiprotein complex that examines the quality of and determines the availability of messenger RNAs (mRNAs) posttranscriptionally. Four proteins, MAGO, Y14, eIF4AIII and BTZ, function as core components of the EJC. The mechanisms of their interactions and the biological indications of these interactions are still poorly understood in plants. A new mutation, hap1-2. leads to premature pollen death and a reduced seed production in Arabidopsis. This mutation introduces a viable truncated transcript AtMagoΔC...
2016: PloS One
Emilie Elvira-Matelot, Florian Bardou, Federico Ariel, Vincent Jauvion, Nathalie Bouteiller, Ivan Le Masson, Jun Cao, Martin D Crespi, Hervé Vaucheret
RNA quality control (RQC) eliminates aberrant RNAs based on their atypical structure, whereas posttranscriptional gene silencing (PTGS) eliminates both aberrant and functional RNAs through the sequence-specific action of short interfering RNAs (siRNAs). The Arabidopsis thaliana mutant smd1b was identified in a genetic screen for PTGS deficiency, revealing the involvement of SmD1, a component of the Smith (Sm) complex, in PTGS. The smd1a and smd1b single mutants are viable, but the smd1a smd1b double mutant is embryo-lethal, indicating that SmD1 function is essential...
February 2016: Plant Cell
Petra Björk, Jan-Olov Persson, Lars Wieslander
Eukaryotic gene expression requires the ordered association of numerous factors with precursor messenger RNAs (premRNAs)/messenger RNAs (mRNAs) to achieve efficiency and regulation. Here, we use the Balbiani ring (BR) genes to demonstrate the temporal and spatial association of the exon junction complex (EJC) core with gene-specific endogenous premRNAs and mRNAs. The EJC core components bind cotranscriptionally to BR premRNAs during or very rapidly after splicing. The EJC core does not recruit the nonsense-mediated decay mediaters UPF2 and UPF3 until the BR messenger RNA protein complexes (mRNPs) enter the interchromatin...
October 12, 2015: Journal of Cell Biology
Orit Shaul
Nonsense-mediated mRNA Decay (NMD) is a eukaryotic quality-control mechanism that governs the stability of both aberrant and normal transcripts. Although plant and mammalian NMD share great similarity, they differ in certain mechanistic and regulatory aspects. Whereas SMG6 (from Caenorhabditis elegans 'suppressor with morphogenetic effect on genitalia')-catalyzed endonucleolytic cleavage is a prominent step in mammalian NMD, plant NMD targets are degraded by an SMG7-induced exonucleolytic pathway. Both mammalian and plant NMD are downregulated by stress, thereby enhancing the expression of defense response genes...
November 2015: Trends in Plant Science
Feng He, Allan Jacobson
Nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that monitors cytoplasmic mRNA translation and targets mRNAs undergoing premature translation termination for rapid degradation. From yeasts to humans, activation of NMD requires the function of the three conserved Upf factors: Upf1, Upf2, and Upf3. Here, we summarize the progress in our understanding of the molecular mechanisms of NMD in several model systems and discuss recent experiments that address the roles of Upf1, the principal regulator of NMD, in the initial targeting and final degradation of NMD-susceptible mRNAs...
2015: Annual Review of Genetics
Evgeniya Degtiar, Adi Fridman, Dror Gottlieb, Karina Vexler, Irina Berezin, Ronit Farhi, Linoy Golani, Orit Shaul
Nonsense-mediated-decay (NMD) is a eukaryotic RNA surveillance mechanism that controls the levels of both aberrant and normal transcripts. The regulation of this process is not well understood. The Arabidopsis NMD factor UPF3 is regulated by a negative feedback-loop that targets its own transcript for NMD. We investigated the functional significance of this control for the overall regulation of NMD in Arabidopsis. For this, we tested the ability of NMD-sensitive and -insensitive forms of UPF3, expressed under the control of UPF3 promoter, to complement NMD functionality in NMD-mutant plants and investigated their impact in wild-type (WT) plants...
April 30, 2015: Nucleic Acids Research
Julia Contreras, Victoria Begley, Sandra Macias, Eduardo Villalobo
Nonsense-mediated decay recognises mRNAs containing premature termination codons. One of its components, UPF3, is a molecular link bridging through its binding to the exon junction complex nonsense-mediated decay and splicing. In protists UPF3 has not been identified yet. We report that Paramecium tetraurelia bears an UPF3 gene and that it has a role in nonsense-mediated decay. Interestingly, the identified UPF3 has not conserved the essential amino acids required to bind the exon junction complex. Though, our data indicates that this ciliate bears genes coding for core proteins of the exon junction complex...
December 2014: Research in Microbiology
Alper Celik, Stephanie Kervestin, Allan Jacobson
Nonsense-mediated mRNA decay (NMD) is one of three regulatory mechanisms that monitor the cytoplasm for aberrant mRNAs. NMD is usually triggered by premature translation termination codons that arise from mutations, transcription errors, or inefficient splicing, but which also occur in transcripts with alternately spliced isoforms or upstream open reading frames, or in the context of long 3'-UTRs. This surveillance pathway requires detection of the nonsense codon by the eukaryotic release factors (eRF1 and eRF3) and the activities of the Upf proteins, but the exact mechanism by which a nonsense codon is recognized as premature, and the individual roles of the Upf proteins, are poorly understood...
July 2015: Biochimie
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