keyword
MENU ▼
Read by QxMD icon Read
search

Splicing

keyword
https://www.readbyqxmd.com/read/29457796/h3b-8800-an-orally-available-small-molecule-splicing-modulator-induces-lethality-in-spliceosome-mutant-cancers
#1
Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney, Michael Thomas, Anant A Agrawal, Benjamin Caleb, Alfredo Csibi, Eckley Sean, Peter Fekkes, Craig Karr, Virginia Klimek, George Lai, Linda Lee, Pavan Kumar, Stanley Chun-Wei Lee, Xiang Liu, Crystal Mackenzie, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Shouyong Peng, Sudeep Prajapati, Justin Taylor, Teng Teng, John Wang, Markus Warmuth, Huilan Yao, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith, Silvia Buonamici
Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells...
February 19, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29457789/a-common-variant-alters-scn5a-mir-24-interaction-and-associates-with-heart-failure-mortality
#2
Xiaoming Zhang, Jin-Young Yoon, Michael Morley, Jared M McLendon, Kranti A Mapuskar, Rebecca Gutmann, Haider Mehdi, Heather L Bloom, Samuel C Dudley, Patrick T Ellinor, Alaa A Shalaby, Raul Weiss, W H Wilson Tang, Christine S Moravec, Madhurmeet Singh, Anne L Taylor, Clyde W Yancy, Arthur M Feldman, Dennis M McNamara, Kaikobad Irani, Douglas R Spitz, Patrick Breheny, Kenneth B Margulies, Barry London, Ryan L Boudreau
SCN5A encodes the voltage-gated Na+ channel NaV1.5 that is responsible for depolarization of the cardiac action potential and rapid intercellular conduction. Mutations disrupting the SCN5A coding sequence cause inherited arrhythmias and cardiomyopathy, and single-nucleotide polymorphisms (SNPs) linked to SCN5A splicing, localization, and function associate with heart failure-related sudden cardiac death. However, the clinical relevance of SNPs that modulate SCN5A expression levels remains understudied. We recently generated a transcriptome-wide map of microRNA (miR) binding sites in human heart, evaluated their overlap with common SNPs, and identified a synonymous SNP (rs1805126) adjacent to a miR-24 site within the SCN5A coding sequence...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29456968/alternative-splicing-of-differentiated-myeloid-cell-transcripts-after-infection-by-anaplasma-phagocytophilum-impacts-a-selective-group-of-cellular-programs
#3
J Stephen Dumler, Sara H Sinclair, Amol C Shetty
Eukaryotic proteome diversity exceeds that encoded within individual genes, and results in part from alternative splicing events of pre-messenger RNA. The diversity of these splicing events can shape the outcome in development and differentiation of normal tissues, and is important in pathogenic circumstances such as cancer and some heritable conditions. A role for alternative splicing of eukaryotic genes in response to viral and intracellular bacterial infections has only recently been recognized, and plays an important role in providing fitness for microbial survival, while potentially enhancing pathogenicity...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29456105/marine-bis-%C3%AE-pyrone-polypropionates-of-onchidione-family-and-their-effects-on-the-xbp1-gene-expression
#4
Zhen-Fang Zhou, Xiao-Lu Li, Li-Gong Yao, Jia Li, Margherita Gavagnin, Yue-Wei Guo
Two additional new members of the onchidione family, 16-epi-onchidione (1) and 4-epi-onchidione (2), co-occurring with six previously reported bis-γ-pyrone polypropionates including onchidione (3), were isolated from the marine pulmonate Onchidium sp. Their structures were determined by extensive spectroscopic analysis and by comparison with 3 and onchidione-related derivatives. The absolute configuration of 1 was established by X-ray diffraction analysis employing graphite monochromated Cu Kα radiation (λ = 0...
February 8, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29454968/ess2-bridges-transcriptional-regulators-and-spliceosomal-complexes-via-distinct-interacting-domains
#5
Ichiro Takada, Megumi Tsuchiya, Kaori Yanaka, Shinya Hidano, Sayuri Takahashi, Takashi Kobayashi, Hidesato Ogawa, Sinichi Nakagawa, Makoto Makishima
Transcription and pre-mRNA splicing are complex, coupled processes that involve transcriptional co-regulators. Ess2 (also termed Dgcr14) is a nuclear protein that enhances the transcriptional activity of retinoic acid receptor-related orphan receptor gamma/gamma-t (Rorγ/γt). Ess2 is also a component of the spliceosomal C complex (containing U2, U5 and U6 snRNAs). However, the domains in Ess2 that function in splicing and transcription have not been identified. To elucidate the roles of Ess2 in splicing and transcription, we performed RNA immunoprecipitation (RIP) assays to detect Ess2-interacting snRNAs...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29454830/the-discrepancy-function-of-nlrc5-isoforms-in-antiviral-and-antibacterial-immune-responses
#6
Lu Cao, Xiao Man Wu, Yi Wei Hu, Na Na Xue, Pin Nie, Ming Xian Chang
NOD-like receptors (NLRs) are a family of intracellular pattern recognition receptors (PRRs) that play critical roles in innate immunity against pathogens infection. NLRC5, the largest member of NLR family, has been characterized as a regulator of innate immunity and MHC class I expression. Alternative splicing of NLRC5 is only reported in human and zebrafish. However, the function of NLRC5 isoforms in the innate immune responses remains unknown. In the present study, we report the functional characterization of zfNLRC5a and zfNLRC5d, two splicing isoforms of zebrafish NLRC5...
February 15, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29454087/multi-step-splicing-of-sphingomyelin-synthase-linear-and-circular-rnas
#7
Ivan B Filippenkov, Olga Yu Sudarkina, Svetlana A Limborska, Lyudmila V Dergunova
The SGMS1 gene encodes the enzyme sphingomyelin synthase 1 (SMS1), which is involved in the regulation of lipid metabolism, apoptosis, intracellular vesicular transport and other significant processes. The SGMS1 gene is located on chromosome 10 and has a size of 320 kb. Previously, we showed that dozens of alternative transcripts of the SGMS1 gene are present in various human tissues. In addition to mRNAs that provide synthesis of the SMS1 protein, this gene participates in the synthesis of non-coding transcripts, including circular RNAs (circRNAs), which include exons of the 5'-untranslated region (5'-UTR) and are highly represented in the brain...
February 14, 2018: Gene
https://www.readbyqxmd.com/read/29453336/alternative-splicing-of-alcam-enables-tunable-regulation-of-cell-cell-adhesion-through-differential-proteolysis
#8
Katie E Hebron, Elizabeth Y Li, Shanna A Arnold Egloff, Ariana K von Lersner, Chase Taylor, Joep Houkes, David K Flaherty, Adel Eskaros, Thomas P Stricker, Andries Zijlstra
While many adhesion receptors are known to influence tumor progression, the mechanisms by which they dynamically regulate cell-cell adhesion remain elusive. We previously identified Activated Leukocyte Cell Adhesion Molecule (ALCAM) as a clinically relevant driver of metastasis and hypothesized that a tunable mechanism of ectodomain shedding regulates its contribution to dissemination. To test this hypothesis, we examined an under-explored ALCAM splice variant (ALCAM-Iso2) and demonstrated that loss of the membrane-proximal region of ALCAM (exon 13) increased metastasis four-fold...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29453314/ar-expression-in-breast-cancer-ctcs-associates-with-bone-metastases
#9
Nicola Aceto, Aditya Bardia, Ben S Wittner, Maria C Donaldson, Ryan O'Keefe, Amanda Engstrom, Francesca Bersani, Yu Zheng, Valentine Comaills, Kira Niederhoffer, Huili Zhu, Olivia MacKenzie, Toshi Shioda, Dennis Sgroi, Ravi Kapur, David T Ting, Beverly Moy, Sridhar Ramaswamy, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran
Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing (RNA-seq) was performed of circulating tumor cells (CTCs) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452748/knockout-of-human-muscle-genes-revealed-by-large-scale-whole-exome-studies
#10
Stefano Schiaffino
Large scale whole-exome sequence studies have revealed that a number of individuals from different populations have predicted loss-of-function of different genes due to nonsense, frameshift, or canonical splice-site mutations. Surprisingly, many of these mutations do not apparently show the deleterious phenotypic consequences expected from gene knockout. These homozygous null mutations, when confirmed, can provide insight into human gene function and suggest novel approaches to correct gene dysfunction, as the lack of the expected disease phenotype may reflect the existence of modifier genes that reveal potential therapeutic targets...
February 10, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29452658/corrigendum-to-quantification-of-type-ii-procollagen-splice-forms-using-alternative-transcript-qpcr-at-qpcr-matrix-biol-31-2012-412-420
#11
Audrey McAlinden, Kyu-Hwan Shim, Louisa Wirthlin, Soumya Ravindran, Thomas M Hering
No abstract text is available yet for this article.
January 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29452611/pmca2-pump-mutations-and-hereditary-deafness
#12
REVIEW
Mario Bortolozzi, Fabio Mammano
Hair cells of the inner ear detect sound stimuli, inertial or gravitational forces by deflection of their apical stereocilia. A small number of stereociliary cation-selective mechanotransduction (MET) channels admit K+ and Ca2+ ions into the cytoplasm promoting hair cell membrane depolarization and, consequently, neurotransmitter release at the cell basolateral pole. Ca2+ influx into the stereocilia compartment is counteracted by the unusual w/a splicing variant of plasma-membrane calcium-pump isoform 2 (PMCA2) which, unlike other PMCA2 variants, increases only marginally its activity in response to a rapid variation of the cytoplasmic free Ca2+ concentration ([Ca2+ ]c )...
January 10, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29452578/clinical-and-genetic-study-of-20-patients-from-china-with-cornelia-de-lange-syndrome
#13
Mingyan Hei, Xiangyu Gao, Lingqian Wu
BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare congenital syndrome with no racial difference. The objective of this study is to report the clinical characteristics and genetic study of 20 CdLS cases from China. METHODS: This is an observational study. Suspected patients were referred for further confirmation, clinical treatment, and genetic testing under voluntary condition. Demographic data and family history, data of clinical manifestations including facial dysmorphism and developmental delay of each patient were collected...
February 16, 2018: BMC Pediatrics
https://www.readbyqxmd.com/read/29452398/predominant-patterns-of-splicing-evolution-on-human-chimpanzee-and-macaque-evolutionary-lineages
#14
Jieyi Xiong, Jiang Xi, Angeliki Ditsiou, Yang Gao, Jing Sun, Elijah D Lowenstein, Shuyun Huang, Philipp Khaitovich
Although splicing is widespread and evolves rapidly among species, the mechanisms driving this evolution, as well as its functional implications, are not yet fully understood. We analyzed the evolution of splicing patterns based on transcriptome data from five tissues of humans, chimpanzees, rhesus macaques, and mice. In total, 1,526 exons and exon sets from 1,236 genes showed significant splicing differences among primates. More than 60% of these differences represent constitutive-to-alternative exon transitions while an additional 25% represent changes in exon inclusion frequency...
February 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29452304/the-chondrocyte-channelome-a-narrative-review
#15
Ali Mobasheri, Csaba Matta, Ilona Uzielienè, Emma Budd, Pablo Martín-Vasallo, Eiva Bernotiene
Chondrocytes are the main cells in the extracellular matrix of articular cartilage and possess a highly differentiated phenotype that is the hallmark of the unique physiological functions of this specialised load-bearing connective tissue. The plasma membrane of articular chondrocytes contains a rich and diverse complement of membrane proteins, known as the membranome, which defines the cell surface phenotype of the cells. The membranome is a key target of pharmacological agents and is important for chondrocyte function...
February 13, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29452161/c33-a-cells-transfected-with-e6-i-or-e6-ii-the-short-forms-of-hpv-16-e6-displayed-opposite-effects-on-cisplatin-induced-apoptosis
#16
Carolina E Vaisman, Oscar Del Moral-Hernandez, Samadhi Moreno-Campuzano, Elena Aréchaga-Ocampo, Raul Bonilla-Moreno, Israel Garcia-Aguiar, Leticia Cedillo-Barron, Jaime Berumen, Porfirio Nava, Nicolas Villegas-Sepúlveda
The HPV-16 E6/E7 bicistronic immature transcript produces 4 mature RNAs: the unspliced HPV-16 E6/E7 pre-mRNA product and 3 alternatively spliced mRNAs. The 3 spliced mRNAs encode short forms of the E6 oncoprotein, namely E6*I, E6*II and E6^E7. In this study we showed that transfection of C-33A cells with monocistronic constructs of these cDNAs fused to GFP, produced different effects on apoptosis, after the treatment with cisplatin. Transfection of C-33A cells with the full-length E6-GFP oncoprotein resulted in a 50% decrease in cell death, while the transfection with the E6*I-GFP construct showed only a 25% of diminution of cell death, compared to the control cells...
February 13, 2018: Virus Research
https://www.readbyqxmd.com/read/29451486/-uveal-melanoma-a-model-disease-for-splicing-alterations-and-oncogenesis
#17
Samar Alsafadi, Lenha Mobuchon, Manuel Rodrigues, Marc-Henri Stern
Uveal melanoma is a rare cancer in adults, whose highly stereotyped oncogenic events have been decrypted over the last decade. Its epidemiological, genetic and transcriptional features make it a remarkable model of oncogenesis. Malignant transformation involves almost mutually exclusive alteration of fundamental biologic pathways, including chromatin regulation with inactivation of BAP1, splicing with mutations of SF3B1 or translation with mutations of EIF1AX. Uveal melanoma analyses unraveled the splicing defect due to SF3B1 mutations...
February 2018: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/29450990/splicing-site-recognition-by-synergy-of-three-domains-in-splicing-factor-rbm10
#18
Pedro Serrano, John A Hammond, Michael Geralt, Kurt Wüthrich
Splicing factor RBM10 and its close homologues RBM5 and RBM6 govern the splicing of oncogenes such as Fas, NUMB, and Bcl-X. The molecular architecture of these proteins includes zinc fingers (ZnFs) and RNA recognition motifs (RRMs). Three of these domains in RBM10 that constitute the RNA binding part of this splicing factor were found to individually bind RNAs with micromolar affinities. It was thus of interest to further investigate the structural basis of the well-documented high-affinity RNA recognition by RMB10...
February 16, 2018: Biochemistry
https://www.readbyqxmd.com/read/29450424/cd44v6-increases-gastric-cancer-malignant-phenotype-by-modulating-adipose-stromal-cell-mediated-ecm-remodeling
#19
Bianca N Lourenço, Nora L Springer, Daniel Ferreira, Carla Oliveira, Pedro L Granja, Claudia Fischbach
CD44, an abundantly expressed adhesion molecule, and its alternative splice variants have been associated with tumorigenesis and metastasis. In the context of gastric cancer (GC), de novo expression of CD44 variant 6 (CD44v6) is found in more than 60% of GCs, but its role in the pathogenesis and progression of this type of cancer remains unclear. Using a combination of media conditioning experiments and decellularized extracellular matrices (ECMs), this study investigates the hypothesis that CD44v6 overexpression enhances tumor cell malignant behavior by modulating stromal cell-mediated ECM remodeling...
February 16, 2018: Integrative Biology: Quantitative Biosciences From Nano to Macro
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
#20
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
keyword
keyword
16620
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"