keyword
MENU ▼
Read by QxMD icon Read
search

Nonsense suppression

keyword
https://www.readbyqxmd.com/read/29764417/upf1-silenced-cellular-model-systems-for-screening-of-read-through-agents-active-on-%C3%AE-0-39-thalassemia-point-mutation
#1
Francesca Salvatori, Mariangela Pappadà, Giulia Breveglieri, Elisabetta D'Aversa, Alessia Finotti, Ilaria Lampronti, Roberto Gambari, Monica Borgatti
BACKGROUND: Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β0 39 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons...
May 15, 2018: BMC Biotechnology
https://www.readbyqxmd.com/read/29671102/phosphorylation-by-prp4-kinase-releases-the-self-inhibition-of-fgprp31-in-fusarium-graminearum
#2
Xuli Gao, Ju Zhang, Chaoni Song, Kangyi Yuan, Jianhua Wang, Qiaojun Jin, Jin-Rong Xu
Prp31 is one of the key tri-snRNP components essential for pre-mRNA splicing although its exact molecular function is not well studied. In a previous study, suppressor mutations were identified in the PRP31 ortholog in two spontaneous suppressors of Fgprp4 mutant deleted of the only kinase of the spliceosome in Fusarium graminearum. To further characterize the function of FgPrp31 and its relationship with FgPrp4 kinase, in this study we identified additional suppressor mutations in FgPrp31 and determined the suppressive effects of selected mutations...
April 18, 2018: Current Genetics
https://www.readbyqxmd.com/read/29581437/orthogonality-of-pyrrolysine-trna-in-the-xenopus-oocyte
#3
Daniel T Infield, John D Lueck, Jason D Galpin, Grace D Galles, Christopher A Ahern
Chemical aminoacylation of orthogonal tRNA allows for the genetic encoding of a wide range of synthetic amino acids without the need to evolve specific aminoacyl-tRNA synthetases. This method, when paired with protein expression in the Xenopus laevis oocyte expression system, can extract atomic scale functional data from a protein structure to advance the study of membrane proteins. The utility of the method depends on the orthogonality of the tRNA species used to deliver the amino acid. Here, we report that the pyrrolysyl tRNA (pylT) from Methanosarcina barkeri fusaro is orthogonal and highly competent for genetic code expansion experiments in the Xenopus oocyte...
March 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29514868/identifying-rna-splicing-factors-using-ift-genes-in-chlamydomonas-reinhardtii
#4
Huawen Lin, Zhengyan Zhang, Carlo Iomini, Susan K Dutcher
Intraflagellar transport moves proteins in and out of flagella/cilia and it is essential for the assembly of these organelles. Using whole-genome sequencing, we identified splice site mutations in two IFT genes, IFT81 ( fla9 ) and IFT121 ( ift121-2 ), which lead to flagellar assembly defects in the unicellular green alga Chlamydomonas reinhardtii The splicing defects in these ift mutants are partially corrected by mutations in two conserved spliceosome proteins, DGR14 and FRA10. We identified a dgr14 deletion mutant, which suppresses the 3' splice site mutation in IFT81 , and a frameshift mutant of FRA10 , which suppresses the 5' splice site mutation in IFT121 Surprisingly, we found dgr14-1 and fra10 mutations suppress both splice site mutations...
March 2018: Open Biology
https://www.readbyqxmd.com/read/29507327/generation-and-characterization-of-a-hypothyroidism-rat-model-with-truncated-thyroid-stimulating-hormone-receptor
#5
Jianqiang Yang, Ning Yi, Junhui Zhang, Wen He, Di He, Wanwan Wu, Shuyang Xu, Feng Li, Guoping Fan, Xianmin Zhu, Zhigang Xue, Wensheng Zhou
Thyroid stimulating hormone receptor (TSHR), a G-protein-coupled receptor, is important for thyroid development and growth. In several cases, frameshift and/or nonsense mutations in TSHR were found in the patients with congenital hypothyroidism (CH), however they have not been functionally studied in an animal model. In the present work, we generated a unique Tshr Df/Df rat model that recapitulates the phenotypes in TSHR Y444X patient by CRISPR/Cas genome editing technology. In this rat model, TSHR is truncated at the second transmembrane domain, leading to CH phenotypes as what was observed in the patients, including dwarf, thyroid aplasia, infertility, TSH resistant as well as low serum thyroid hormone levels...
March 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29487844/managing-bardet-biedl-syndrome-now-and-in-the-future
#6
REVIEW
Elizabeth Forsythe, Joanna Kenny, Chiara Bacchelli, Philip L Beales
Bardet-Biedl syndrome is a rare autosomal recessive multisystem disorder caused by defects in genes encoding for proteins that localize to the primary cilium/basal body complex. Twenty-one disease-causing genes have been identified to date. It is one of the most well-studied conditions in the family of diseases caused by defective cilia collectively known as ciliopathies. In this review, we provide an update on diagnostic developments, clinical features, and progress in the management of Bardet-Biedl syndrome...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29449800/robustness-and-vulnerability-of-the-autoregulatory-system-that-maintains-nuclear-tdp-43-levels-a-trade-off-hypothesis-for-als-pathology-based-on-in-silico-data
#7
Akihiro Sugai, Taisuke Kato, Akihide Koyama, Yuka Koike, Sou Kasahara, Takuya Konno, Tomohiko Ishihara, Osamu Onodera
Abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm and its disappearance from the nucleus are pathological features of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) and are directly involved in the pathogenesis of these conditions. TDP-43 is an essential nuclear protein that readily aggregates in a concentration-dependent manner. Therefore, cells must strictly maintain an appropriate amount of nuclear TDP-43. In one relevant maintenance mechanism, TDP-43 binds to its pre-mRNA and promotes alternative splicing, resulting in mRNA degradation via nonsense-mediated mRNA decay...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29404996/using-amber-and-ochre-nonsense-codons-to-code-two-different-noncanonical-amino-acids-in-one-protein-gene
#8
Jeffery M Tharp, Wenshe R Liu
In Escherichia coli, conventional amber and ochre stop codons can be separately targeted by engineered amber-suppressing Methanocaldococcus jannaschii tyrosyl-tRNA synthetase-tRNAPyl and ochre-suppressing Methanosarcina maezi pyrrolysyl-tRNA synthetase-tRNAPyl pairs for coding two different noncanonical amino acids in one protein gene. Here, we describe the application of this approach to produce a protein with two distinct chemical functionalites which can be selectively labeled with two fluorescent dyes.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29388273/secretion-of-wild-type-factor-ix-upon-readthrough-over-f9-pre-peptide-nonsense-mutations-causing-hemophilia-b
#9
Mattia Ferrarese, Maria Francesca Testa, Dario Balestra, Francesco Bernardi, Mirko Pinotti, Alessio Branchini
Pre-peptide regions of secreted proteins display wide sequence variability, even among highly homologous proteins such as coagulation factors, and are intracellularly removed, thus potentially favoring secretion of wild-type proteins upon suppression of nonsense mutations (translational readthrough). As models we selected F9 nonsense mutations with readthrough-favorable features affecting the pre-peptide and pro-peptide regions of coagulation factor IX (FIX), which cause hemophilia B (HB). Only the p.Gly21Ter (c...
May 2018: Human Mutation
https://www.readbyqxmd.com/read/29359503/a-general-strategy-to-access-structural-information-at-atomic-resolution-in-polyglutamine-homorepeats
#10
Annika Urbanek, Anna Morató, Frédéric Allemand, Elise Delaforge, Aurélie Fournet, Matija Popovic, Stephane Delbecq, Nathalie Sibille, Pau Bernadó
Homorepeat (HR) proteins are involved in key biological processes and multiple pathologies, however their high-resolution characterization has been impaired due to their homotypic nature. To overcome this problem, we have developed a strategy to isotopically label individual glutamines within HRs by combining nonsense suppression and cell-free expression. Our method has enabled the NMR investigation of huntingtin exon1 with a 16-residue polyglutamine (poly-Q) tract, and the results indicate the presence of an N-terminal α-helix at near neutral pH that vanishes towards the end of the HR...
March 26, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29334995/antisense-suppression-of-the-nonsense-mediated-decay-factor-upf3b-as-a-potential-treatment-for-diseases-caused-by-nonsense-mutations
#11
Lulu Huang, Audrey Low, Sagar S Damle, Melissa M Keenan, Steven Kuntz, Susan F Murray, Brett P Monia, Shuling Guo
BACKGROUND: About 11% of all human genetic diseases are caused by nonsense mutations that generate premature translation termination codons (PTCs) in messenger RNAs (mRNA). PTCs not only lead to the production of truncated proteins, but also often result in  decreased mRNA abundance due to  nonsense-mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an attractive therapeutic approach for the treatment of diseases caused by nonsense mutations, NMD also regulates the expression of 10-20% of the normal transcriptome...
January 15, 2018: Genome Biology
https://www.readbyqxmd.com/read/29321549/probing-the-molecular-basis-of-herg-drug-block-with-unnatural-amino-acids
#12
Logan C Macdonald, Robin Y Kim, Harley T Kurata, David Fedida
Repolarization of the cardiac action potential is primarily mediated by two voltage-dependent potassium currents: I Kr and I Ks . The voltage-gated potassium channel that gives rise to I Kr , Kv 11.1 (hERG), is uniquely susceptible to high-affinity block by a wide range of drug classes. Pore residues Tyr652 and Phe656 are critical to potent drug interaction with hERG. It is considered that the molecular basis of this broad-spectrum drug block phenomenon occurs through interactions specific to the aromatic nature of the side chains at Tyr652 and Phe656...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29309033/nonsense-mrna-suppression-via-nonstop-decay
#13
Joshua A Arribere, Andrew Z Fire
Nonsense-mediated mRNA decay is the process by which mRNAs bearing premature stop codons are recognized and cleared from the cell. While considerable information has accumulated regarding recognition of the premature stop codon, less is known about the ensuing mRNA suppression. During the characterization of a second, distinct translational surveillance pathway (nonstop mRNA decay), we trapped intermediates in nonsense mRNA degradation. We present data in support of a model wherein nonsense-mediated decay funnels into the nonstop decay pathway in Caenorhabditis elegans ...
January 8, 2018: ELife
https://www.readbyqxmd.com/read/29285795/ataluren-driven-restoration-of-shwachman-bodian-diamond-syndrome-protein-function-in-shwachman-diamond-syndrome-bone-marrow-cells
#14
Valentino Bezzerri, Donatella Bardelli, Jacopo Morini, Antonio Vella, Simone Cesaro, Claudio Sorio, Andrea Biondi, Cesare Danesino, Piero Farruggia, Baroukh Maurice Assael, Giovanna D'amico, Marco Cipolli
Shwachman-Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndrome (MDS) and are at higher risk of developing acute myeloid leukemia (AML)...
August 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29242642/targeting-mutant-p53-for-efficient-cancer-therapy
#15
REVIEW
Vladimir J N Bykov, Sofi E Eriksson, Julie Bianchi, Klas G Wiman
The tumour suppressor gene TP53 is the most frequently mutated gene in cancer. Wild-type p53 can suppress tumour development by multiple pathways. However, mutation of TP53 and the resultant inactivation of p53 allow evasion of tumour cell death and rapid tumour progression. The high frequency of TP53 mutation in tumours has prompted efforts to restore normal function of mutant p53 and thereby trigger tumour cell death and tumour elimination. Small molecules that can reactivate missense-mutant p53 protein have been identified by different strategies, and two compounds are being tested in clinical trials...
February 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29153836/post-transcriptional-regulation-of-de-novo-lipogenesis-by-mtorc1-s6k1-srpk2-signaling
#16
Gina Lee, Yuxiang Zheng, Sungyun Cho, Cholsoon Jang, Christina England, Jamie M Dempsey, Yonghao Yu, Xiaolei Liu, Long He, Paola M Cavaliere, Andre Chavez, Erik Zhang, Meltem Isik, Anthony Couvillon, Noah E Dephoure, T Keith Blackwell, Jane J Yu, Joshua D Rabinowitz, Lewis C Cantley, John Blenis
mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling...
December 14, 2017: Cell
https://www.readbyqxmd.com/read/29128743/the-suppression-of-premature-termination-codons-and-the-repair-of-splicing-mutations-in-cftr
#17
REVIEW
Yifat S Oren, Iwona M Pranke, Batsheva Kerem, Isabelle Sermet-Gaudelus
Premature termination codons (PTC) originate from nucleotide substitution introducing an in-frame PTC. They induce truncated, usually non-functional, proteins, degradation of the PTC containing transcripts by the nonsense-mediated decay (NMD) pathway and abnormal exon skipping. Readthrough compounds facilitate near cognate amino-acyl-tRNA incorporation, leading potentially to restoration of a functional full-length protein. Splicing mutations can lead to aberrantly spliced transcripts by creating a cryptic splice site or destroying a normal site...
June 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29109183/mutation-and-suppressor-analysis-of-the-essential-lipopolysaccharide-transport-protein-lpta-reveals-strategies-to-overcome-severe-outer-membrane-permeability-defects-in-escherichia-coli
#18
Federica A Falchi, Elisa A Maccagni, Simone Puccio, Clelia Peano, Cristina De Castro, Angelo Palmigiano, Domenico Garozzo, Alessandra M Martorana, Alessandra Polissi, Gianni Dehò, Paola Sperandeo
In Gram-negative bacteria, lipopolysaccharide (LPS) contributes to the robust permeability barrier of the outer membrane (OM), preventing the entry of toxic molecules, such as detergents and antibiotics. LPS is transported from the inner membrane (IM) to the OM by the Lpt multiprotein machinery. Defects in LPS transport compromise LPS assembly at the OM and result in increased antibiotic sensitivity. LptA is a key component of the Lpt machine that interacts with the IM protein LptC and chaperones LPS through the periplasm...
January 15, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29106929/gentamicin-induced-readthrough-and-nonsense-mediated-mrna-decay-of-serpinb7-nonsense-mutant-transcripts
#19
Yuka Ohguchi, Toshifumi Nomura, Shotaro Suzuki, Masae Takeda, Toshinari Miyauchi, Osamu Mizuno, Satoru Shinkuma, Yasuyuki Fujita, Osamu Nemoto, Kota Ono, W H Irwin McLean, Hiroshi Shimizu
Nagashima-type palmoplantar keratosis (NPPK) is an autosomal recessive skin disorder with a high, unmet medical need that is caused by mutations in SERPINB7. Almost all NPPK patients carry the founder nonsense mutation c.796C>T (p.Arg266Ter) in the last exon of SERPINB7. Here we sought to determine whether topical nonsense-suppression (readthrough) therapy using gentamicin is applicable to NPPK. First, we demonstrated that gentamicin enhanced readthrough activity in cells transfected with SERPINB7 cDNA carrying the mutation and promoted full-length SERPINB7 protein synthesis in NPPK keratinocytes...
April 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29081953/defining-the-current-scope-and-limitations-of-dual-noncanonical-amino-acid-mutagenesis-in-mammalian-cells
#20
Yunan Zheng, Partha Sarathi Addy, Raja Mukherjee, Abhishek Chatterjee
The ability to site-specifically incorporate two distinct noncanonical amino acids (ncAAs) into the proteome of a mammalian cell with high fidelity and efficiency will have many enabling applications. It would require the use of two different engineered aminoacyl-tRNA synthetase (aaRS)/tRNA pairs, each suppressing a distinct nonsense codon, and which cross-react neither with each other, nor with their counterparts from the host cell. Three different aaRS/tRNA pairs have been developed so far to expand the genetic code of mammalian cells, which can be potentially combined in three unique ways to drive site-specific incorporation of two distinct ncAAs...
October 1, 2017: Chemical Science
keyword
keyword
13619
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"