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Alternative splicing

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https://www.readbyqxmd.com/read/29165996/itop-q-an-intelligent-tool-for-top-down-proteomics-quantitation-us-ing-dyamond-algorithm
#1
Hui-Yin Chang, Ching-Tai Chen, Chu-Ling Ko, Yi-Ju Chen, Yu-Ju Chen, Wen-Lian Hsu, Chiun-Gung Juo, Ting-Yi Sung
Top-down proteomics using liquid chromatogram coupled with mass spectrometry has been increasingly applied for analyzing intact proteins to study genetic variation, alternative splicing, and post-translational modifications (PTMs) of the proteins (proteoforms). However, only a few tools have been developed for charge state deconvolution, monoisotopic/average molecular weight determination and quantitation of proteoforms from LC-MS1 spectra. Though Decon2LS and MASH Suite Pro have been available to provide intra-spectrum charge state deconvolution and quantitation, manual processing is still required to quantify proteoforms across multiple MS1 spectra...
November 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29164313/genome-wide-analysis-of-a-recently-active-retrotransposon-au-sine-in-wheat-content-distribution-within-subgenomes-and-chromosomes-and-gene-associations
#2
Danielle Keidar, Chen Doron, Khalil Kashkush
Here, we show that Au SINE elements have strong associations with protein-coding genes in wheat. Most importantly Au SINE insertion within introns causes allelic variation and might induce intron retention. The impact of transposable elements (TEs) on genome structure and function is intensively studied in eukaryotes, especially in plants where TEs can reach up to 90% of the genome in some cases, such as in wheat. Here, we have performed a genome-wide in-silico analysis using the updated publicly available genome draft of bread wheat (T...
November 21, 2017: Plant Cell 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
#3
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/29163049/tagging-of-endogenous-bk-channels-with-a-fluorogen-activating-peptide-reveals-%C3%AE-4-mediated-control-of-channel-clustering-in-cerebellum
#4
Christopher P Pratt, Dika A Kuljis, Gregg E Homanics, Jianjun He, Dmytro Kolodieznyi, Srikanth Dudem, Mark A Hollywood, Alison L Barth, Marcel P Bruchez
BK channels are critical regulators of neuronal activity, controlling firing, neurotransmitter release, cerebellar function, and BK channel mutations have been linked to seizure disorders. Modulation of BK channel gating is well characterized, regulated by accessory subunit interactions, intracellular signaling pathways, and membrane potential. In contrast, the role of intracellular trafficking mechanisms in controlling BK channel function, especially in live cells, has been less studied. Fluorogen-activating peptides (FAPs) are well-suited for trafficking and physiological studies due to the binding of malachite green (MG)-based dyes with sub-nanomolar affinity to the FAP, resulting in bright, photostable, far-red fluorescence...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29162908/human-canonical-cd157-bst1-is-an-alternatively-spliced-isoform-masking-a-previously-unidentified-primate-specific-exon-included-in-a-novel-transcript
#5
Enza Ferrero, Nicola Lo Buono, Simona Morone, Rossella Parrotta, Cecilia Mancini, Alfredo Brusco, Alice Giacomino, Stefania Augeri, Antonio Rosal-Vela, Sonia García-Rodríguez, Mercedes Zubiaur, Jaime Sancho, Alessandra Fiorio Pla, Ada Funaro
CD157/Bst1 is a dual-function receptor and β-NAD(+)-metabolizing ectoenzyme of the ADP-ribosyl cyclase family. Expressed in human peripheral blood neutrophils and monocytes, CD157 interacts with extracellular matrix components and regulates leukocyte diapedesis via integrin-mediated signalling in inflammation. CD157 also regulates cell migration and is a marker of adverse prognosis in epithelial ovarian cancer and pleural mesothelioma. One form of CD157 is known to date: the canonical sequence of 318 aa from a 9-exon transcript encoded by BST1 on human chromosome 4...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162741/nuclear-hyaluronidase-2-drives-alternative-splicing-of-cd44-pre-mrna-to-determine-profibrotic-or-antifibrotic-cell-phenotype
#6
Adam C Midgley, Sebastian Oltean, Vincent Hascall, Emma L Woods, Robert Steadman, Aled O Phillips, Soma Meran
The cell surface protein CD44 is involved in diverse physiological processes, and its aberrant function is linked to various pathologies such as cancer, immune dysregulation, and fibrosis. The diversity of CD44 biological activity is partly conferred by the generation of distinct CD44 isoforms through alternative splicing. We identified an unexpected function for the ubiquitous hyaluronan-degrading enzyme, hyaluronidase 2 (HYAL2), as a regulator of CD44 splicing. Standard CD44 is associated with fibrotic disease, and its production is promoted through serine-arginine-rich (SR) protein-mediated exon exclusion...
November 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/29162484/differential-homologous-desensitization-of-the-human-histamine-h3-receptors-of-445-and-365-amino-acids-expressed-in-cho-k1-cells
#7
Ana-Maricela García-Gálvez, Juan Escamilla-Sánchez, Catalina Flores-Maldonado, Rubén-Gerardo Contreras, Juan-Manuel Arias, José-Antonio Arias-Montaño
Histamine H3 receptors (H3Rs) signal through Gαi/o proteins and are found in neuronal cells as auto- and hetero-receptors. Alternative splicing of the human H3R (hH3R) originates 20 isoforms, and the mRNAs of two receptors of 445 and 365 amino acids (hH3R445 and hH3R365) are widely expressed in the human brain. We previously showed that the hH3R445 stably expressed in CHO-K1 cells experiences homologous desensitization. The hH3R365 lacks 80 residues in the third intracellular loop, and in this work we therefore studied whether this isoform also experiences homologous desensitization and the possible differences with the hH3R445...
November 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29161012/top-down-proteomics-ready-for-prime-time
#8
Bifan Chen, Kyle A Brown, Ziqing Lin, Ying Ge
In the post-genomics era, the study of proteins is critical for understanding cellular functions at the molecular level.1-5 Beyond the genetic code, the human proteome is greatly diversified by various genetic variations, alternative splicing of RNA transcripts, and post-translational modifi-cations (PTMs).6,7 In 2013, the term "proteoform" was designated to describe "all of the different molecular forms in which the protein product of a single gene can be found",6 clearing up the confusion in nomenclature and joining research efforts to develop methodologies for pro-teoform characterization...
November 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29158982/genome-wide-in-silico-identification-of-membrane-bound-transcription-factors-in-plant-species
#9
Shixiang Yao, Lili Deng, Kaifang Zeng
Membrane-bound transcription factors (MTFs) are located in cellular membranes due to their transmembrane domains. In plants, proteolytic processing is considered to be the main mechanism for MTF activation, which ensures the liberation of MTFs from membranes and further their translocation into the nucleus to regulate gene expression; this process skips both the transcriptional and translational stages, and thus it guarantees the prompt responses of plants to various stimuli. Currently, information concerning plant MTFs is limited to model organisms, including Arabidopsis thaliana and Oryza sativa, and little is known in other plant species at the genome level...
2017: PeerJ
https://www.readbyqxmd.com/read/29157056/the-intron-landscape-of-the-mtdna-cytb-gene-among-the-ascomycota-introns-and-intron-encoded-open-reading-frames
#10
Tuhin K Guha, Alvan Wai, Sahra-Taylor Mullineux, Georg Hausner
Fungal mitochondrial genes are frequently noted for the presence of introns. These introns are self-splicing and can be assigned to either group I or II introns and they can encode open reading frames (ORFs). This study examines the introns present within the cytochrome b (cytb) gene of ascomycetes fungi. Cytochrome b gene sequences were sampled from GenBank and supplemented with our own data for species of Leptographium and Ophiostoma. Group I introns were encountered most frequently, many encoding either LAGLIDADG or GIY-YIG homing endonucleases (HEs)...
November 20, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/29156833/targeting-aggressive-prostate-cancer-associated-cd44v6-using-phage-display-selected-peptides
#11
Ying Peng, Austin R Prater, Susan L Deutscher
There is a crucial need to identify new biomarkers associated with aggressive prostate cancer (PCa) including those associated with cancer stem cells (CSCs). CD44v6, generated by alternative splicing of CD44, has been proposed as a CSC biomarker due to its correlation with aggressive PCa disease. We hypothesized that phage display selected peptides that target CD44v6 may serve as theranostic agents for aggressive PCa. Here, a 15 amino acid peptide ("PFT") was identified by affinity selection against a peptide derived from the v6 region of CD44v6...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156002/specific-g-quadruplex-ligands-modulate-the-alternative-splicing-of-bcl-x
#12
Carika Weldon, Justine G Dacanay, Vijay Gokhale, Peda Venkat L Boddupally, Isabelle Behm-Ansmant, Glenn A Burley, Christiane Branlant, Laurence H Hurley, Cyril Dominguez, Ian C Eperon
Sequences with the potential to form RNA G-quadruplexes (G4s) are common in mammalian introns, especially in the proximity of the 5' splice site (5'SS). However, the difficulty of demonstrating that G4s form in pre-mRNA in functional conditions has meant that little is known about their effects or mechanisms of action. We have shown previously that two G4s form in Bcl-X pre-mRNA, one close to each of the two alternative 5'SS. If these G4s affect splicing but are in competition with other RNA structures or RNA binding proteins, then ligands that stabilize them would increase the proportion of Bcl-X pre-mRNA molecules in which either or both G4s had formed, shifting Bcl-X splicing...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29155138/hpv16-e5-is-produced-from-an-hpv16-early-mrna-spliced-from-sd226-to-sa3358
#13
Kersti Nilsson, Christopher Norberg, Ann-Kristin Mossberg, Stefan Schwartz
The HPV16 E5 open reading frame (ORF) is present on the majority of all alternatively spliced HPV16 mRNAs, but it is currently unknown how well it is translated into E5 protein. To identify HPV16 mRNAs that are efficiently translated into E5, we have generated cDNA plasmids expressing individual, alternatively spliced HPV16 mRNAs with the potential to produce E5. By replacing the E5 ORF with sLuc, we could quantitate sLuc and determine how well each cDNA was translated. Our results showed that the upstream E1 and E7 AUGs inhibited translation of the E5 ORF and revealed that only one HPV16 mRNA produced high levels of E5...
November 16, 2017: Virus Research
https://www.readbyqxmd.com/read/29154754/functional-divergence-of-paralogous-transcription-factors-supported-the-evolution-of-biomineralization-in-echinoderms
#14
Jian Ming Khor, Charles A Ettensohn
Alx1 is a pivotal transcription factor in a gene regulatory network that controls skeletogenesis throughout the echinoderm phylum. We performed a structure-function analysis of sea urchin Alx1 using a rescue assay and identified a novel, conserved motif (Domain 2) essential for skeletogenic function. The paralogue of Alx1, Alx4, was not functionally interchangeable with Alx1, but insertion of Domain 2 conferred robust skeletogenic function on Alx4. We used cross-species expression experiments to show that Alx1 proteins from distantly related echinoderms are not interchangeable, although the sequence and function of Domain 2 are highly conserved...
November 20, 2017: ELife
https://www.readbyqxmd.com/read/29150831/the-extracellular-membrane-proximal-domain-of-membrane-bound-ige-restricts-b-cell-activation-by-limiting-b-cell-antigen-receptor-surface-expression
#15
Kanika Vanshylla, Felipe Opazo, Konrad Gronke, Jürgen Wienands, Niklas Engels
Immunoglobulin E (IgE) antibodies are key mediators of allergic reactions. Due to their potentially harmful anaphylactic properties their production is tightly regulated. The membrane-bound isoform of IgE (mIgE), which is an integral component of the B cell antigen receptor, has been shown to be critical for the regulation of IgE responses in mice. In primate species including humans, mIgE can be expressed in two isoforms that are produced by alternative splicing of the primary ε Ig heavy chain transcript, and differ in the absence or presence of an extracellular membrane-proximal domain (EMPD) consisting of 52 amino acids...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29150548/defense-against-reactive-carbonyl-species-involves-at-least-three-subcellular-compartments-where-individual-components-of-the-system-respond-to-cellular-sugar-status
#16
Jessica Schmitz, Isabell C Dittmar, Jörn D Brockmann, Marc Schmidt, Meike Hüdig, Alessandro W Rossoni, Veronica G Maurino
Methylglyoxal (MGO) and glyoxal (GO) are toxic reactive carbonyl species generated as by-products of glycolysis. The pre-emption pathway for detoxification of these products, the glyoxalase (GLX) system, involves two consecutive reactions catalyzed by GLXI and GLXII. In Arabidopsis thaliana, the GLX system is encoded by three homologs of GLXI and three homologs of GLXII, from which several predicted GLXI and GLXII isoforms can be derived through alternative splicing. We identified the physiologically relevant splice forms using sequencing data and demonstrated that the resulting isoforms have different subcellular localizations...
November 17, 2017: Plant Cell
https://www.readbyqxmd.com/read/29149730/divergence-of-insulin-superfamily-ligands-receptors-and-igf-binding-proteins-in-marine-versus-freshwater-stickleback-evidence-of-selection-in-known-and-novel-genes
#17
Tim Pellissier, Hend Al Nafea, Sara V Good
Three-spine stickleback (Gasterosteus aculeatus) is a teleost model for understanding genetic, physiological and morphological changes accompanying freshwater (FW) adaptation. There is growing evidence that the insulin superfamily plays important roles in traits involved in marine and FW adaptation. We performed a candidate gene analysis to look for evidence of selection on 33 insulin superfamily ligand-receptor genes and insulin-like growth factor binding proteins (Igfbp's) in stickleback. Using genotype data from 11 marine and 10 FW populations, we calculated the number of SNPs per site in regulatory and intronic regions, the number of synonymous and nonsynonymous mutations in coding regions, Wright's fixation index (Fst), and performed t-tests to identify SNPs with divergent genotype frequencies between marine/FW versus Atlantic/Pacific populations...
November 10, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/29149504/mybl1-rearrangements-and-myb-amplification-in-breast-adenoid-cystic-carcinomas-lacking-the-myb-nfib-fusion-gene
#18
Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer (TNBC), has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression...
November 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29149296/comparative-transcriptomics-of-five-high-altitude-vertebrates-and-their-low-altitude-relatives
#19
Qianzi Tang, Yiren Gu, Xuming Zhou, Long Jin, Jiuqiang Guan, Rui Liu, Jing Li, Kereng Long, Shilin Tian, Tiandong Che, Silu Hu, Yan Liang, Xuemei Yang, Xuan Tao, Zhijun Zhong, Guosong Wang, Xiaohui Chen, Diyan Li, Jideng Ma, Xun Wang, Miaomiao Mai, An'an Jiang, Xiaolin Luo, Xuebin Lv, Vadim N Gladyshev, Xuewei Li, Mingzhou Li
Background: Species living at high altitude are subject to strong selective pressures due to inhospitable environments (e.g., hypoxia, low temperature, high solar radiation, and lack of biological production), making these species valuable models for comparative analyses of local adaptation. Studies that examined high-altitude adaptation identified a vast array of rapidly evolving genes that characterize the dramatic phenotypic changes in high-altitude animals. However, how high-altitude environment shapes gene expression programs remains largely unknown...
November 15, 2017: GigaScience
https://www.readbyqxmd.com/read/29149056/characterization-of-ovine-a3z1-restriction-properties-against-small-ruminant-lentiviruses-srlvs
#20
Lorena de Pablo-Maiso, Idoia Glaria, Helena Crespo, Estanislao Nistal-Villán, Valgerdur Andrésdóttir, Damián de Andrés, Beatriz Amorena, Ramsés Reina
Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties...
November 17, 2017: Viruses
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