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https://www.readbyqxmd.com/read/29626148/new-insights-into-the-interplay-between-the-translation-machinery-and-nonsense-mediated-mrna-decay-factors
#1
REVIEW
Etienne Raimondeau, Joshua C Bufton, Christiane Schaffitzel
Faulty mRNAs with a premature stop codon (PTC) are recognized and degraded by nonsense-mediated mRNA decay (NMD). Recognition of a nonsense mRNA depends on translation and on the presence of NMD-enhancing or the absence of NMD-inhibiting factors in the 3'-untranslated region. Our review summarizes our current understanding of the molecular function of the conserved NMD factors UPF3B and UPF1, and of the anti-NMD factor Poly(A)-binding protein, and their interactions with ribosomes translating PTC-containing mRNAs...
April 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29596649/the-loss-of-smg1-causes-defects-in-quality-control-pathways-in-physcomitrella-patens
#2
James P B Lloyd, Daniel Lang, Andreas D Zimmer, Barry Causier, Ralf Reski, Brendan Davies
Nonsense-mediated mRNA decay (NMD) is important for RNA quality control and gene regulation in eukaryotes. NMD targets aberrant transcripts for decay and also directly influences the abundance of non-aberrant transcripts. In animals, the SMG1 kinase plays an essential role in NMD by phosphorylating the core NMD factor UPF1. Despite SMG1 being ubiquitous throughout the plant kingdom, little is known about its function, probably because SMG1 is atypically absent from the genome of the model plant, Arabidopsis thaliana...
March 27, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29510736/microrna-1468-promotes-tumor-progression-by-activating-ppar-%C3%AE-mediated-akt-signaling-in-human-hepatocellular-carcinoma
#3
Zhikui Liu, Yufeng Wang, Changwei Dou, Liankang Sun, Qing Li, Liang Wang, Qiuran Xu, Wei Yang, Qingguang Liu, Kangsheng Tu
BACKGROUND: Accumulating evidence confirm that aberrant microRNAs (miRNAs) expression contributes to hepatocellular carcinoma (HCC) development and progression. Previous study reported that miR-1468 showed an up-regulated tendency and might be a potential prognostic biomarker in HCC samples derived from TCGA database. However, the role of miR-1468 and its underlying mechanisms involved in the growth and metastasis of HCC remain poorly investigated. METHODS: CCK-8, EdU, colony formation and flow cytometry were used to determine proliferation, cell cycle progression and apoptosis of HCC cells in vitro...
March 6, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29504902/terius-accurate-prediction-of-lncrna-via-high-throughput-sequencing-data-representing-rna-binding-protein-association
#4
Seo-Won Choi, Jin-Wu Nam
BACKGROUND: LncRNAs are long regulatory non-coding RNAs, some of which are arguably predicted to have coding potential. Despite coding potential classifiers that utilize ribosome profiling data successfully detected actively translated regions, they are less sensitive to lncRNAs. Furthermore, lncRNA annotation can be susceptible to false positives obtained from 3' untranslated region (UTR) fragments of mRNAs. RESULTS: To lower these limitations in lncRNA annotation, we present a novel tool TERIUS that provides a two-step filtration process to distinguish between bona fide and false lncRNAs...
February 19, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29382845/htlv-1-tax-plugs-and-freezes-upf1-helicase-leading-to-nonsense-mediated-mrna-decay-inhibition
#5
Francesca Fiorini, Jean-Philippe Robin, Joanne Kanaan, Malgorzata Borowiak, Vincent Croquette, Hervé Le Hir, Pierre Jalinot, Vincent Mocquet
Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD...
January 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29378013/a-conserved-structural-element-in-the-rna-helicase-upf1-regulates-its-catalytic-activity-in-an-isoform-specific-manner
#6
Manjeera Gowravaram, Fabien Bonneau, Joanne Kanaan, Vincent D Maciej, Francesca Fiorini, Saurabh Raj, Vincent Croquette, Hervé Le Hir, Sutapa Chakrabarti
The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay (NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the molecular mechanisms of its catalytic activity and regulation. In this study, we examine features of the UPF1 core and identify a structural element that adopts different conformations in the various nucleotide- and RNA-bound states of UPF1. We demonstrate, using biochemical and single molecule assays, that this structural element modulates UPF1 catalytic activity and thereby refer to it as the regulatory loop...
March 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29377675/anti-prion-systems-in-yeast-and-inositol-polyphosphates
#7
Reed Brendon Wickner, Evgeny E Bezsonov, Moonil Son, Mathieu Ducatez, Morgan Dewilde, Herman K Edskes
The amyloid-based yeast prions are folded in-register parallel beta sheet polymers. Each prion can exist in a wide array of variants, with different biological properties resulting from different self-propagating amyloid conformations. Yeast has several anti-prion systems, acting in normal cells (without protein overexpression or deficiency). Some anti-prion proteins partially block prion formation (Ssb1,2p - ribosome-associated Hsp70s), others cure a large portion of prion variants that arise (Btn2p, Cur1p, Hsp104 - a disaggregase, Siw14p, Upf1,2,3p - nonsense-mediated decay proteins) and others prevent prion-induced pathology (Sis1p - essential cytoplasmic Hsp40)...
January 29, 2018: Biochemistry
https://www.readbyqxmd.com/read/29358398/nonsense-mediated-mrna-decay-factors-cure-most-psi-prion-variants
#8
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
https://www.readbyqxmd.com/read/29348139/dissecting-the-functions-of-smg5-smg7-and-pnrc2-in-nonsense-mediated-mrna-decay-of-human-cells
#9
Pamela Nicholson, Asimina Gkratsou, Christoph Josi, Martino Colombo, Oliver Mühlemann
The term "nonsense-mediated mRNA decay" (NMD) originally described the degradation of mRNAs with premature translation-termination codons (PTCs), but its meaning has recently been extended to be a translation-dependent post-transcriptional regulator of gene expression affecting 3%-10% of all mRNAs. The degradation of NMD target mRNAs involves both exonucleolytic and endonucleolytic pathways in mammalian cells. While the latter is mediated by the endonuclease SMG6, the former pathway has been reported to require a complex of SMG5-SMG7 or SMG5-PNRC2 binding to UPF1...
April 2018: RNA
https://www.readbyqxmd.com/read/29339519/evidence-for-convergent-evolution-of-sine-directed-staufen-mediated-mrna-decay
#10
Bronwyn A Lucas, Eitan Lavi, Lily Shiue, Hana Cho, Sol Katzman, Keita Miyoshi, Mikiko C Siomi, Liran Carmel, Manuel Ares, Lynne E Maquat
Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29282598/upf-proteins-highly-conserved-factors-involved-in-nonsense-mrna-mediated-decay
#11
REVIEW
Puneet Gupta, Yan-Ruide Li
Over 10% of genetic diseases are caused by mutations that introduce a premature termination codon in protein-coding mRNA. Nonsense-mediated mRNA decay (NMD) is an essential cellular pathway that degrades these mRNAs to prevent the accumulation of harmful partial protein products. NMD machinery is also increasingly appreciated to play a role in other essential cellular functions, including telomere homeostasis and the regulation of normal mRNA turnover, and is misregulated in numerous cancers. Hence, understanding and designing therapeutics targeting NMD is an important goal in biomedical science...
February 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29236296/rna-decay-factor-upf1-promotes-protein-decay-a-hidden-talent
#12
REVIEW
Terra-Dawn M Plank, Miles F Wilkinson
The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay (NMD) pathway. Feng et al. now report a new function for UPF1-it is an E3 ubiquitin ligase that specifically promotes the decay of a key pro-muscle transcription factor: MYOD. UPF1 achieves this through its RING-like domain, which confers ubiquitin E3 ligase activity. Feng et al. provide evidence that the ability of UPF1 to destabilize MYOD represses myogenesis. In the future, it will be important to define other protein substrates of UPF1-driven ubiquitination and to determine whether this biochemical activity is responsible for some of UPF1's previously defined biological functions, including in development and stress responses...
January 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29236259/identifying-cellular-nonsense-mediated-mrna-decay-nmd-targets-immunoprecipitation-of-phosphorylated-upf1-followed-by-rna-sequencing-p-upf1-rip-seq
#13
Tatsuaki Kurosaki, Mainul Hoque, Lynne E Maquat
Recent progress in the technology of transcriptome-wide high-throughput sequencing has revealed that nonsense-mediated mRNA decay (NMD) targets ~10% of physiologic transcripts for the purpose of tuning gene expression in response to various environmental conditions. Regardless of the eukaryote studied, NMD requires the ATP-dependent RNA helicase upframeshift 1 (UPF1). It was initially thought that cellular NMD targets could be defined by their binding to steady-state UPF1, which is largely hypophosphorylated...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29235495/identification-of-nonsense-mediated-mrna-decay-pathway-as-a-critical-regulator-of-p53-isoform-%C3%AE
#14
Lauren E Cowen, Yi Tang
Human TP53 gene encodes the tumor suppressor p53 and, via alternative splicing, the p53β and γ isoforms. Numerous studies have shown that p53β/γ can modulate p53 functions and are critically involved in regulation of cellular response to stress conditions. However, it is not fully understood how the β and γ isoforms are regulated following splicing. Using gene targeting and RNAi, we showed that depletion of the nonsense-mediated mRNA decay (NMD) factor SMG7 or UPF1 significantly induced p53β but had minimal effect on p53γ...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233693/thermostable-dna-helicase-improves-the-sensitivity-of-digital-pcr
#15
Ryota Hidese, Katsuhiro Kawato, Yukiko Nakura, Ayako Fujiwara, Kiyoshi Yasukawa, Itaru Yanagihara, Shinsuke Fujiwara
DNA/RNA helicases, which catalyze the unwinding of duplex nucleic acids using the energy of ATP hydrolysis, contribute to various biological functions involving DNA or RNA. Euryarchaeota-specific helicase Tk-EshA (superfamily 2) from the hyperthermophilic archaeon Thermococcus kodakarensis has been used to decrease generation of mis-amplified products (noise DNAs) during PCR. In this study, we focused on another type (superfamily 1B) of helicase, Tk-Upf1 (TK0178) from T. kodakarensis, and compared its effectiveness in PCR and digital PCR with that of Tk-EshA...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29192227/conservation-of-nonsense-mediated-mrna-decay-complex-components-throughout-eukaryotic-evolution
#16
Barry Causier, Zhen Li, Riet De Smet, James P B Lloyd, Yves Van de Peer, Brendan Davies
Nonsense-mediated mRNA decay (NMD) is an essential eukaryotic process regulating transcript quality and abundance, and is involved in diverse processes including brain development and plant defenses. Although some of the NMD machinery is conserved between kingdoms, little is known about its evolution. Phosphorylation of the core NMD component UPF1 is critical for NMD and is regulated in mammals by the SURF complex (UPF1, SMG1 kinase, SMG8, SMG9 and eukaryotic release factors). However, since SMG1 is reportedly missing from the genomes of fungi and the plant Arabidopsis thaliana, it remains unclear how UPF1 is activated outside the metazoa...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29164236/posttranscriptional-regulation-of-loxl1-expression-via-alternative-splicing-and-nonsense-mediated-mrna-decay-as-an-adaptive-stress-response
#17
Daniel Berner, Matthias Zenkel, Francesca Pasutto, Ursula Hoja, Panah Liravi, Gabriele C Gusek-Schneider, Friedrich E Kruse, Johannes Schödel, Andre Reis, Ursula Schlötzer-Schrehardt
Purpose: Alternative mRNA splicing coupled to nonsense-mediated decay (NMD) is a common mRNA surveillance pathway also known to dynamically modulate gene expression in response to cellular stress. Here, we investigated the involvement of this pathway in the regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors. Methods: Transcript levels of LOXL1 isoforms were determined in ocular tissues obtained from donor eyes without and with PEX syndrome...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29158530/mrnas-containing-nmd-competent-premature-termination-codons-are-stabilized-and-translated-under-upf1-depletion
#18
Won Kyu Kim, SeongJu Yun, Yujin Kwon, Kwon Tae You, Nara Shin, Jiyoon Kim, Hoguen Kim
mRNAs containing premature termination codons (PTCs) are rapidly degraded through nonsense-mediated mRNA decay (NMD). However, some PTC-containing mRNAs evade NMD, and might generate mutant proteins responsible for various diseases, including cancers. Using PTC-containing human genomic β-globin constructs, we show that a fraction (~30%) of PTC-containing mRNAs expressed from NMD-competent PTC-containing constructs were as stable as their PTC-free counterparts in a steady state. These PTC-containing mRNAs were monosome-enriched and rarely contributed to expression of mutant proteins...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29131639/proteomic-characterization-of-transcription-and-splicing-factors-associated-with-a-metastatic-phenotype-in-colorectal-cancer
#19
Sofía Torres, Irene García-Palmero, Consuelo Marín-Vicente, Rubén A Bartolomé, Eva Calviño, María Jesús Fernández-Aceñero, J Ignacio Casal
We investigated new transcription and splicing factors associated with the metastatic phenotype in colorectal cancer. A concatenated tandem array of consensus transcription factor (TF)-response elements was used to pull down nuclear extracts in two different pairs of colorectal cancer cells, KM12SM/KM12C and SW620/480, genetically related but differing in metastatic ability. Proteins were analyzed by label-free LC-MS and quantified with MaxLFQ. We found 240 proteins showing a significant dysregulation in highly metastatic KM12SM cells relative to nonmetastatic KM12C cells and 257 proteins in metastatic SW620 versus SW480...
January 5, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29122854/the-substrates-of-nonsense-mediated-mrna-decay-in-caenorhabditis-elegans
#20
Virginia S Muir, Audrey P Gasch, Philip Anderson
Nonsense-mediated mRNA decay (NMD) is a conserved pathway that strongly influences eukaryotic gene expression. Inactivating or inhibiting NMD affects the abundance of a substantial fraction of the transcriptome in numerous species. Transcripts whose abundance is altered in NMD-deficient cells may represent either direct substrates of NMD or indirect effects of inhibiting NMD. We present a genome-wide investigation of the direct substrates of NMD in Caenorhabditis elegans Our goals were (i) to identify mRNA substrates of NMD and (ii) to distinguish those mRNAs from others whose abundance is indirectly influenced by the absence of NMD...
January 4, 2018: G3: Genes—Genomes—Genetics
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