keyword
MENU ▼
Read by QxMD icon Read
search

nonsense-mediated decay

keyword
https://www.readbyqxmd.com/read/29781741/slowly-progressive-retinitis-pigmentosa-caused-by-two-novel-mutations-in-the-mak-gene
#1
Joanna Monika Gray, Harry Otway Orlans, Morag Shanks, Penny Clouston, Robert Elvis MacLaren
BACKGROUND: The growing number of clinical trials currently underway for inherited retinal diseases has highlighted the importance of achieving a molecular diagnosis for all new cases presenting to hospital eye services. The male germ cell-associated kinase (MAK) gene encodes a cilium-associated protein selectively expressed in the retina and testis, and has recently been implicated in autosomal recessive retinitis pigmentosa (RP). Whole exome sequencing has previously identified a homozygous Alu insertion in probands with recessive RP and nonsense and missense mutations have also been reported...
May 21, 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/29774201/investigation-of-experimental-factors-that-underlie-brca1-2-mrna-isoform-expression-variation-recommendations-for-utilizing-targeted-rna-sequencing-to-evaluate-potential-spliceogenic-variants
#2
Vanessa L Lattimore, John F Pearson, Margaret J Currie, Amanda B Spurdle, Bridget A Robinson, Logan C Walker
PCR-based RNA splicing assays are commonly used in diagnostic and research settings to assess the potential effects of variants of uncertain clinical significance in BRCA1 and BRCA2 . The Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium completed a multicentre investigation to evaluate differences in assay design and the integrity of published data, raising a number of methodological questions associated with cell culture conditions and PCR-based protocols. We utilized targeted RNA-seq to re-assess BRCA1 and BRCA2 mRNA isoform expression patterns in lymphoblastoid cell lines (LCLs) previously used in the multicentre ENIGMA study...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29770900/insights-into-mutation-effect-in-three-poikiloderma-with-neutropenia-patients-by-transcript-analysis-and-disease-evolution-of-reported-patients-with-the-same-pathogenic-variants
#3
Elisa A Colombo, Nursel H Elcioglu, Claudio Graziano, Pamela Farinelli, Elisabetta Di Fede, Iria Neri, Elena Facchini, Mariangela Greco, Cristina Gervasini, Lidia Larizza
PURPOSE: Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients...
May 16, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29769535/systematic-pan-cancer-analysis-of-somatic-allele-frequency
#4
Liam Spurr, Muzi Li, Nawaf Alomran, Qianqian Zhang, Paula Restrepo, Mercedeh Movassagh, Chris Trenkov, Nerissa Tunnessen, Tatiyana Apanasovich, Keith A Crandall, Nathan Edwards, Anelia Horvath
Imbalanced expression of somatic alleles in cancer can suggest functional and selective features, and can therefore indicate possible driving potential of the underlying genetic variants. To explore the correlation between allele frequency of somatic variants and total gene expression of their harboring gene, we used the unique data set of matched tumor and normal RNA and DNA sequencing data of 5523 distinct single nucleotide variants in 381 individuals across 10 cancer types obtained from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768215/mechanism-of-nonsense-mediated-mrna-decay-stimulation-by-splicing-factor-srsf1
#5
Isabel Aznarez, Tomoki T Nomakuchi, Jaclyn Tetenbaum-Novatt, Mohammad Alinoor Rahman, Oliver Fregoso, Holly Rees, Adrian R Krainer
The splicing factor SRSF1 promotes nonsense-mediated mRNA decay (NMD), a quality control mechanism that degrades mRNAs with premature termination codons (PTCs). Here we show that transcript-bound SRSF1 increases the binding of NMD factor UPF1 to mRNAs while in, or associated with, the nucleus, bypassing UPF2 recruitment and promoting NMD. SRSF1 promotes NMD when positioned downstream of a PTC, which resembles the mode of action of exon junction complex (EJC) and NMD factors. Moreover, splicing and/or EJC deposition increase the effect of SRSF1 on NMD...
May 15, 2018: Cell Reports
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
#6
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/29755318/arc-3-utr-splicing-leads-to-dual-and-antagonistic-effects-in-fine-tuning-arc-expression-upon-bdnf-signaling
#7
Chiara Paolantoni, Simona Ricciardi, Veronica De Paolis, Chinenye Okenwa, Caterina Catalanotto, Maria T Ciotti, Antonino Cattaneo, Carlo Cogoni, Corinna Giorgi
Activity-regulated cytoskeletal associated protein (Arc) is an immediate-early gene critically involved in synaptic plasticity and memory consolidation. Arc mRNA is rapidly induced by synaptic activation and a portion is locally translated in dendrites where it modulates synaptic strength. Being an activity-dependent effector of homeostatic balance, regulation of Arc is uniquely tuned to result in short-lived bursts of expression. Cis -Acting elements that control its transitory expression post-transcriptionally reside primarily in Arc mRNA 3' UTR...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29715486/human-papilloma-virus-hpv-18-proteins-e6-and-e7-up-regulate-abc-transporters-in-oropharyngeal-carcinoma-involvement-of-the-nonsense-mediated-decay-nmd-pathway
#8
Juan Pablo Rigalli, Matthias Reichel, Guillermo Nicolás Tocchetti, Tasmin Reuter, Gerhard Dyckhoff, Christel Herold-Mende, Johanna Weiss
Oropharyngeal cancer incidence increased dramatically in the last decades, being infection with human papillomaviruses (HPV) a determinant of this trend. Concerning etiology, treatment response and prognosis, HPV+ and HPV- oropharyngeal cancers constitute different disease entities. The underlying molecular background is not completely understood. ATP-binding cassette (ABC) transporters mediate the efflux of anticancer drugs and are regulated by changes in the intracellular milieu. Furthermore, a role in cancer pathogenesis besides drug transport was reported...
April 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29691655/loss-of-function-mutations-in-vars-encoding-cytoplasmic-valyl-trna-synthetase-cause-microcephaly-seizures-and-progressive-cerebral-atrophy
#9
Joshi Stephen, Sheela Nampoothiri, Aditi Banerjee, Nathanial J Tolman, Josef Martin Penninger, Ullrich Elling, Chukwuma A Agu, John D Burke, Kalpana Devadathan, Rajesh Kannan, Yan Huang, Peter J Steinbach, Susan A Martinis, William A Gahl, May Christine V Malicdan
Progressive microcephaly and neurodegeneration are genetically heterogenous conditions, largely associated with genes that are essential for the survival of neurons. In this study, we interrogate the genetic etiology of two siblings from a non-consanguineous family with severe early onset of neurological manifestations. Whole exome sequencing identified novel compound heterozygous mutations in VARS that segregated with the proband: a missense (c.3192G>A; p.Met1064Ile) and a splice site mutation (c.1577-2A>G)...
April 24, 2018: Human Genetics
https://www.readbyqxmd.com/read/29688405/a-homozygous-mutation-p-arg2167trp-in-frem2-causes-isolated-cryptophthalmos
#10
Qian Yu, Bingying Lin, Shangqian Xie, Song Gao, Wei Li, Yizhi Liu, Hongwei Wang, Danping Huang, Zhi Xie
Cryptophthalmos (CO, MIM: 123570) is rare congenital anomalies of eyelid formation, which can occur alone or in combination with multiple congenital anomalies as part of Fraser syndrome (FS) or Manitoba Oculotrichoanal (MOTA) syndrome. Causal mutations have been identified for these syndromes but not in the isolated cases. Here, we described two patients from two unrelated Chinese families: one with unilateral isolated CO, while the other with unilateral CO and renal agenesis. A novel homozygous mutation (c...
April 24, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29683372/modulating-the-expression-of-chtop-a-versatile-regulator-of-gene-specific-transcription-and-mrna-export
#11
Keiichi Izumikawa, Hideaki Ishikawa, Richard J Simpson, Nobuhiro Takahashi
Chtop binds competitively to the arginine methyltransferases PRMT1 and PRMT5, thereby promoting the asymmetric or symmetric methylation of arginine residues, respectively. In cooperation with PRMT1, Chtop activates transcription of certain gene groups, such as the estrogen-inducible genes in breast cancer cells, the 5-hydroxymethylcytosine-modified genes involved in glioblastomagenesis, or the Zbp-89-dependent genes in erythroleukemia cells. Chtop also represses expression of the fetal γ-globin gene. In addition, Chtop is a component of the TREX complex that links transcription elongation to mRNA export...
April 23, 2018: RNA Biology
https://www.readbyqxmd.com/read/29681101/a-patient-with-peripheral-demyelinating-neuropathy-central-dysmyelinating-leukodystrophy-waardenburg-syndrome-and-severe-hypoganglionosis-associated-with-a-novel-sox10-mutation
#12
Yuko Akutsu, Kentaro Shirai, Akira Takei, Yudai Goto, Tomohiro Aoyama, Akimitu Watanabe, Masatoshi Imamura, Takashi Enokizono, Tatsuyuki Ohto, Tetsuo Hori, Keiko Suzuki, Masaharu Hayashi, Kouji Masumoto, Ken Inoue
In this report, we present the case of a female infant with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH) associated with a novel frameshift mutation (c.842dupT) in exon 5, the last exon of SOX10. She had severe hypoganglionosis in the small intestine and entire colon, and suffered from frequent enterocolitis. The persistence of ganglion cells made both the diagnosis and treatment difficult in the neonatal period. She also showed hypopigmentation of the irises, hair and skin, bilateral sensorineural deafness with hypoplastic inner year, severe demyelinating neuropathy with hypotonia, and diffuse brain hypomyelination...
May 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29672715/the-nonstop-decay-and-the-rna-silencing-systems-operate-cooperatively-in-plants
#13
István Szádeczky-Kardoss, Tibor Csorba, Andor Auber, Anita Schamberger, Tünde Nyikó, János Taller, Tamás I Orbán, József Burgyán, Dániel Silhavy
Translation-dependent mRNA quality control systems protect the protein homeostasis of eukaryotic cells by eliminating aberrant transcripts and stimulating the decay of their protein products. Although these systems are intensively studied in animals, little is known about the translation-dependent quality control systems in plants. Here, we characterize the mechanism of nonstop decay (NSD) system in Nicotiana benthamiana model plant. We show that plant NSD efficiently degrades nonstop mRNAs, which can be generated by premature polyadenylation, and stop codon-less transcripts, which are produced by endonucleolytic cleavage...
April 17, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29663678/three-patients-with-desanto-shinawi-syndrome-further-phenotypic-delineation
#14
Tomoko Uehara, Takashi Ishige, Shigeto Hattori, Hiroshi Yoshihashi, Michinori Funato, Yu Yamaguchi, Toshiki Takenouchi, Kenjiro Kosaki
Somatic truncating variants of the WAC gene have been observed in patients with hematologic malignancies. Furthermore, de novo heterozygous constitutional pathogenic variants of WAC have recently been shown to cause a syndromic form of intellectual disability, DeSanto-Shinawi syndrome. It is unknown whether the constitutional pathogenic variants observed in the intellectual disability syndrome overlap with the somatic pathogenic variants observed in hematologic abnormalities. Herein, we report three patients with constitutional truncating variants of WAC in an attempt to address the above questions...
April 16, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29656860/truncating-variants-in-naa15-are-associated-with-variable-levels-of-intellectual-disability-autism-spectrum-disorder-and-congenital-anomalies
#15
Hanyin Cheng, Avinash V Dharmadhikari, Sylvia Varland, Ning Ma, Deepti Domingo, Robert Kleyner, Alan F Rope, Margaret Yoon, Asbjørg Stray-Pedersen, Jennifer E Posey, Sarah R Crews, Mohammad K Eldomery, Zeynep Coban Akdemir, Andrea M Lewis, Vernon R Sutton, Jill A Rosenfeld, Erin Conboy, Katherine Agre, Fan Xia, Magdalena Walkiewicz, Mauro Longoni, Frances A High, Marjon A van Slegtenhorst, Grazia M S Mancini, Candice R Finnila, Arie van Haeringen, Nicolette den Hollander, Claudia Ruivenkamp, Sakkubai Naidu, Sonal Mahida, Elizabeth E Palmer, Lucinda Murray, Derek Lim, Parul Jayakar, Michael J Parker, Stefania Giusto, Emanuela Stracuzzi, Corrado Romano, Jennifer S Beighley, Raphael A Bernier, Sébastien Küry, Mathilde Nizon, Mark A Corbett, Marie Shaw, Alison Gardner, Christopher Barnett, Ruth Armstrong, Karin S Kassahn, Anke Van Dijck, Geert Vandeweyer, Tjitske Kleefstra, Jolanda Schieving, Marjolijn J Jongmans, Bert B A de Vries, Rolph Pfundt, Bronwyn Kerr, Samantha K Rojas, Kym M Boycott, Richard Person, Rebecca Willaert, Evan E Eichler, R Frank Kooy, Yaping Yang, Joseph C Wu, James R Lupski, Thomas Arnesen, Gregory M Cooper, Wendy K Chung, Jozef Gecz, Holly A F Stessman, Linyan Meng, Gholson J Lyon
N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15...
April 9, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29626148/new-insights-into-the-interplay-between-the-translation-machinery-and-nonsense-mediated-mrna-decay-factors
#16
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
#17
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/29593499/mob2-insufficiency-disrupts-neuronal-migration-in-the-developing-cortex
#18
Adam C O'Neill, Christina Kyrousi, Melanie Einsiedler, Ingo Burtscher, Micha Drukker, David M Markie, Edwin P Kirk, Magdalena Götz, Stephen P Robertson, Silvia Cappello
Disorders of neuronal mispositioning during brain development are phenotypically heterogeneous and their genetic causes remain largely unknown. Here, we report biallelic variants in a Hippo signaling factor- MOB2 -in a patient with one such disorder, periventricular nodular heterotopia (PH). Genetic and cellular analysis of both variants confirmed them to be loss-of-function with enhanced sensitivity to transcript degradation via nonsense mediated decay (NMD) or increased protein turnover via the proteasome...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29580671/intron-retained-transcripts-of-the-spinal-muscular-atrophy-genes-smn1-and-smn2
#19
Nur Imma Fatimah Harahap, Emma Tabe Eko Niba, Mawaddah Ar Rochmah, Yogik Onky Silvana Wijaya, Toshio Saito, Kayoko Saito, Hiroyuki Awano, Ichiro Morioka, Kazumoto Iijima, Poh San Lai, Masafumi Matsuo, Hisahide Nishio, Masakazu Shinohara
BACKGROUND: The SMN genes, SMN1 and SMN2, are highly homologous genes which are related to the development or clinical severity of spinal muscular atrophy. Some alternative splicing patterns of the SMN genes have been well documented. In 2007, an SMN1 transcript with a full sequence of intron 3 was reported as the first intron-retained SMN transcript. METHODS: Intron-retained SMN transcripts in various cells and tissues were studied using reverse transcription (RT)-PCR...
March 23, 2018: Brain & Development
https://www.readbyqxmd.com/read/29566451/dental-implications-in-hajdu-cheney-syndrome-a-novel-case-report-and-review-of-the-literature
#20
Ji Won Lee, Youn Jung Kim, Jenny Kang, Teo Jeon Shin, Hong-Keun Hyun, Young-Jae Kim, Sang-Hoon Lee, Zang Hee Lee, Jung-Wook Kim
OBJECTIVE: To identify the molecular genetic etiology of an individual with a dysmorphic face, unusual teeth mobility and root resorption. SUBJECTS AND METHODS: DNA samples were collected from a trio of family members, and whole exome sequencing was performed. RESULTS: Mutational analysis revealed a de novo mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein without C-terminus, escaping from the nonsense mediated decay system...
March 22, 2018: Oral Diseases
keyword
keyword
54727
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"