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https://www.readbyqxmd.com/read/28978775/up-frameshift-protein-upf1-regulates-neurospora-crassa-circadian-and-diurnal-growth-rhythms
#1
(no author information available yet)
No abstract text is available yet for this article.
October 2017: Genetics
https://www.readbyqxmd.com/read/28950212/p-val19glyfs-21-and-p-leu228-variants-in-the-survival-of-motor-neuron-1-trigger-nonsense-mediated-mrna-decay-causing-the-smn1-ptc-transcripts-degradation
#2
Yu-Jin Qu, Lin Ge, Jin-Li Bai, Yan-Yan Cao, Yu-Wei Jin, Hong Wang, Lan Yang, Fang Song
Spinal Muscular Atrophy (SMA) results from loss-of-function mutations in the survival of motor neuron 1 (SMN1) gene. Our previous research showed that 40% of variants were nonsense or frameshift variants and SMN1 mRNA levels in the patients carrying these variants were significantly decreased. Here we selected one rare variant (p.Val19Glyfs*21) and one common variant (p.Leu228*) to explore the degradation mechanism of mutant transcripts. The levels of full-length (FL)-SMN1 transcripts and SMN protein in the cell lines from the patients with these variants were both significantly reduced (p<0...
September 15, 2017: Mutation Research
https://www.readbyqxmd.com/read/28942451/the-human-rna-surveillance-factor-upf1-modulates-gastric-cancer-progression-by-targeting-long-non-coding-rna-malat1
#3
Li Li, Yingying Geng, Ru Feng, Qinqin Zhu, Bei Miao, Jiang Cao, Sujuan Fei
BACKGROUND/AIMS: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. METHODS: Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28929622/endonuclease-regnase-1-monocyte-chemotactic-protein-1-induced-protein-1-mcpip1-in-controlling-immune-responses-and-beyond
#4
REVIEW
Osamu Takeuchi
The activation of inflammatory cells is controlled at transcriptional and posttranscriptional levels. Posttranscriptional regulation modifies mRNA stability and translation, allowing for elaborate control of proteins required for inflammation, such as proinflammatory cytokines, prostaglandin synthases, cell surface co-stimulatory molecules, and even transcriptional modifiers. Such regulation is important for coordinating the initiation and resolution of inflammation, and is mediated by a set of RNA-binding proteins (RBPs), including Regnase-1, Roquin, Tristetraprolin (TTP), and AU-rich elements/poly(U)-binding/degradation factor 1 (AUF1)...
September 20, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28899899/dual-function-of-upf3b-in-early-and-late-translation-termination
#5
Gabriele Neu-Yilik, Etienne Raimondeau, Boris Eliseev, Lahari Yeramala, Beate Amthor, Aurélien Deniaud, Karine Huard, Kathrin Kerschgens, Matthias W Hentze, Christiane Schaffitzel, Andreas E Kulozik
Nonsense-mediated mRNA decay (NMD) is a cellular surveillance pathway that recognizes and degrades mRNAs with premature termination codons (PTCs). The mechanisms underlying translation termination are key to the understanding of RNA surveillance mechanisms such as NMD and crucial for the development of therapeutic strategies for NMD-related diseases. Here, we have used a fully reconstituted in vitro translation system to probe the NMD proteins for interaction with the termination apparatus. We discovered that UPF3B (i) interacts with the release factors, (ii) delays translation termination and (iii) dissociates post-termination ribosomal complexes that are devoid of the nascent peptide...
September 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28827400/upf1-helicase-promotes-tsn-mediated-mirna-decay
#6
Reyad A Elbarbary, Keita Miyoshi, Omar Hedaya, Jason R Myers, Lynne E Maquat
While microRNAs (miRNAs) regulate the vast majority of protein-encoding transcripts, little is known about how miRNAs themselves are degraded. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway in which the nuclease TSN promotes the decay of miRNAs that contain CA and/or UA dinucleotides. While TSN-mediated degradation of either protein-free or AGO2-loaded miRNAs does not require the ATP-dependent RNA helicase UPF1 in vitro, we report here that cellular TumiD requires UPF1...
July 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28821679/upf1-governs-synaptic-plasticity-through-association-with-a-stau2-rna-granule
#7
Tyson E Graber, Erika Freemantle, Mina N Anadolu, Sarah Hébert-Seropian, Robyn L MacAdam, Unkyung Shin, Huy-Dung Hoang, Tommy Alain, Jean-Claude Lacaille, Wayne S Sossin
Neuronal mRNAs can be packaged in reversibly stalled polysome granules before their transport to distant synaptic locales. Stimulation of synaptic metabotropic glutamate receptors (mGluRs) reactivates translation of these particular mRNAs to produce plasticity-related protein; a phenomenon exhibited during mGluR-mediated LTD. This form of plasticity is deregulated in Fragile X Syndrome, a monogenic form of autism in humans, and understanding the stalling and reactivation mechanism could reveal new approaches to therapies...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28749708/smg-1-kinase-attenuates-mitochondrial-ros-production-but-not-cell-respiration-deficits-during-hyperoxia
#8
Emily A Resseguie, Paul S Brookes, Michael A O'Reilly
PURPOSE: Supplemental oxygen (hyperoxia) used to treat individuals in respiratory distress causes cell injury by enhancing the production of toxic reactive oxygen species (ROS) and inhibiting mitochondrial respiration. The suppressor of morphogenesis of genitalia (SMG-1) kinase is activated during hyperoxia and promotes cell survival by phosphorylating the tumor suppressor p53 on serine 15. Here, we investigate whether SMG-1 and p53 blunt this vicious cycle of progressive ROS production and decline in mitochondrial respiration seen during hyperoxia...
July 27, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28669802/the-rna-surveillance-factor-upf1-represses-myogenesis-via-its-e3%C3%A2-ubiquitin-ligase-activity
#9
Qing Feng, Sujatha Jagannathan, Robert K Bradley
UPF1 is an RNA helicase that orchestrates nonsense-mediated decay and other RNA surveillance pathways. While UPF1 is best known for its basal cytoprotective role in degrading aberrant RNAs, UPF1 also degrades specific, normally occurring mRNAs to regulate diverse cellular processes. Here we describe a role for UPF1 in regulated protein decay, wherein UPF1 acts as an E3 ubiquitin ligase to repress human skeletal muscle differentiation. Suppressing UPF1 accelerates myogenesis, while ectopically increasing UPF1 levels slows myogenesis...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28651017/crystal-structure-of-middle-east-respiratory-syndrome-coronavirus-helicase
#10
Wei Hao, Justyna Aleksandra Wojdyla, Rong Zhao, Ruiyun Han, Rajat Das, Ivan Zlatev, Muthiah Manoharan, Meitian Wang, Sheng Cui
Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs remains unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for drug development. We report here the first structure of full-length coronavirus helicase, MERS-CoV nsp13. MERS-CoV helicase has multiple domains, including an N-terminal Cys/His rich domain (CH) with three zinc atoms, a beta-barrel domain and a C-terminal SF1 helicase core with two RecA-like subdomains...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28648842/pnrc2-regulates-3-utr-mediated-decay-of-segmentation-clock-associated-transcripts-during-zebrafish-segmentation
#11
Thomas L Gallagher, Kiel T Tietz, Zachary T Morrow, Jasmine M McCammon, Michael L Goldrich, Nicolas L Derr, Sharon L Amacher
Vertebrate segmentation is controlled by the segmentation clock, a molecular oscillator that regulates gene expression and cycles rapidly. The expression of many genes oscillates during segmentation, including hairy/Enhancer of split-related (her or Hes) genes, which encode transcriptional repressors that auto-inhibit their own expression, and deltaC (dlc), which encodes a Notch ligand. We previously identified the tortuga (tor) locus in a zebrafish forward genetic screen for genes involved in cyclic transcript regulation and showed that cyclic transcripts accumulate post-splicing in tor mutants...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28600326/up-frameshift-protein-upf1-regulates-neurospora-crassa-circadian-and-diurnal-growth-rhythms
#12
Wu Yilan, Zhang Yin, Sun Yunpeng, Yu Jiali, Wang Peiliang, Ma Huan, Chen Shijunyin, Ma Lizhen, Zhang Dongyang, He Qun, Guo Jinhu
Nonsense-mediated RNA decay (NMD) is a crucial post-transcriptional regulatory mechanism that recognizes and eliminates aberrantly processed transcripts, and mediates the expression of normal gene transcripts. In this study, we report that in the filamentous fungus Neurospora crassa, the NMD factors play a conserved role in regulating the surveillance of NMD targets including premature termination codon (PTC)-containing transcripts and normal transcripts. The circadian rhythms in all of the knockout strains of upf1-3 genes, which encode the Up-frameshift proteins, were aberrant...
August 2017: Genetics
https://www.readbyqxmd.com/read/28554132/the-human-rna-surveillance-factor-up-frameshift-1-inhibits-hepatic-cancer-progression-by-targeting-mrp2-abcc2
#13
Hai Zhang, Yina You, Zhongliang Zhu
Although the roles of Up-frameshift 1 (UPF1) in hepatocellular carcinoma (HCC) have been partly revealed, the detailed mechanisms remain poorly understood. Here, quantitative real-time PCR (qRT-PCR) and immunohistochemistry assays indicated that UPF1 expression was decreased in HCC tissues compared to the corresponding adjacent tissues, and was negatively correlated with MRP2/ABCC2 expression. Cell viability and apoptosis analyses showed that overexpression of UPF1 enhanced HCC cell sensitivity to sorafenib treatment, while knockdown of UPF1 decreased the sensitivity...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28541562/dna-substrate-recognition-and-processing-by-the-full-length-human-upf1-helicase
#14
Saba Dehghani-Tafti, Cyril M Sanders
UPF1 is a conserved helicase required for nonsense-mediated decay (NMD) regulating mRNA stability in the cytoplasm. Human UPF1 (hUPF1) is also needed for nuclear DNA replication. While loss of NMD is tolerated, loss of hUPF1 induces a DNA damage response and cell cycle arrest. We have analysed nucleic acid (NA) binding and processing by full-length hUPF1. hUPF1 unwinds non-B and B-form DNA and RNA substrates in vitro. Unlike many helicases involved in genome stability no hUPF1 binding to DNA structures stabilized by inter-base-pair hydrogen bonding was observed...
July 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28539120/comprehensive-whole-genome-sequence-analyses-yields-novel-genetic-and-structural-insights-for-intellectual-disability
#15
Farah R Zahir, Jill C Mwenifumbo, Hye-Jung E Chun, Emilia L Lim, Clara D M Van Karnebeek, Madeline Couse, Karen L Mungall, Leora Lee, Nancy Makela, Linlea Armstrong, Cornelius F Boerkoel, Sylvie L Langlois, Barbara M McGillivray, Steven J M Jones, Jan M Friedman, Marco A Marra
BACKGROUND: Intellectual Disability (ID) is among the most common global disorders, yet etiology is unknown in ~30% of patients despite clinical assessment. Whole genome sequencing (WGS) is able to interrogate the entire genome, providing potential to diagnose idiopathic patients. METHODS: We conducted WGS on eight children with idiopathic ID and brain structural defects, and their normal parents; carrying out an extensive data analyses, using standard and discovery approaches...
May 24, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28536849/nmd-monitors-translational-fidelity-24-7
#16
REVIEW
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...
May 23, 2017: Current Genetics
https://www.readbyqxmd.com/read/28483531/crucial-role-of-atp-bound-sse1-in-upf1-dependent-degradation-of-the-truncated-product
#17
Takato Sugiyama, Risa Nobuta, Koji Ando, Yasuko Matsuki, Toshifumi Inada
Up-frameshift (Upf) complex facilitates the degradation of aberrant mRNAs containing a premature termination codon (PTC) and its products in yeast. Here we report that Sse1, a member of the Hsp110 family, and Hsp70 play a crucial role in Upf-dependent degradation of the truncated FLAG-Pgk1-300 protein derived from PGK1 mRNA harboring a PTC at codon position 300. Sse1 was required for Upf-dependent rapid degradation of the FLAG-Pgk1-300. FLAG-Pgk1-300 was significantly destabilized in ATP hydrolysis defective sse1-1 mutant cells than in wild type cells...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28461625/transcript-specific-characteristics-determine-the-contribution-of-endo-and-exonucleolytic-decay-pathways-during-the-degradation-of-nonsense-mediated-decay-substrates
#18
Franziska Ottens, Volker Boehm, Christopher R Sibley, Jernej Ule, Niels H Gehring
Nonsense-mediated mRNA decay (NMD) controls gene expression by eliminating mRNAs with premature or aberrant translation termination. Degradation of NMD substrates is initiated by the central NMD factor UPF1, which recruits the endonuclease SMG6 and the deadenylation-promoting SMG5/7 complex. The extent to which SMG5/7 and SMG6 contribute to the degradation of individual substrates and their regulation by UPF1 remains elusive. Here we map transcriptome-wide sites of SMG6-mediated endocleavage via 3' fragment capture and degradome sequencing...
August 2017: RNA
https://www.readbyqxmd.com/read/28444146/nonsense-in-the-testis-multiple-roles-for-nonsense-mediated-decay-revealed-in-male-reproduction
#19
Clinton C MacDonald, Petar N Grozdanov
Nonsense-mediated mRNA decay, or NMD, is a quality control mechanism that identifies cytoplasmic mRNAs containing translational termination (stop) codons in specific contexts-either premature termination codons or unusually long 3΄ untranslated regions (UTRs)-and targets them for degradation. In recent studies, researchers in different labs have knocked out important genes involved in NMD, the up-frameshift genes Upf2 and Upf3a, and one component of chromatoid bodies, the Tudor domain-containing protein Tdrd6, and examined the consequences for spermatogenesis...
May 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28408439/sen1-has-unique-structural-features-grafted-on-the-architecture-of-the-upf1-like-helicase-family
#20
Bronislava Leonaitė, Zhong Han, Jérôme Basquin, Fabien Bonneau, Domenico Libri, Odil Porrua, Elena Conti
The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key role in the termination of non-coding transcription in yeast. Here, we identified the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for transcription termination in vitro and determined the corresponding structure at 1.8 Å resolution. In addition to the catalytic and auxiliary subdomains characteristic of the SF1B family, Sen1 has a distinct and evolutionarily conserved structural feature that "braces" the helicase core...
June 1, 2017: EMBO Journal
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