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https://www.readbyqxmd.com/read/29671412/possible-molecular-markers-for-the-diagnosis-of-pancreatic-ductal-adenocarcinoma
#1
Quan Shen, Miao Yu, Jiang-Kun Jia, Wen-Xi Li, Yu-Wei Tian, Huan-Zhou Xue
BACKGROUND We aimed to identify pivotal genes and pathways involved in pancreatic ductal adenocarcinoma (PDAC), and explore possible molecular markers for the early diagnosis of the disease. MATERIAL AND METHODS The array data of GSE74629, including 34 PDAC samples and 16 healthy samples, was downloaded from GEO (Gene Expression Omnibus) database. Then, the DEGs (differentially expressed genes) in PDAC samples were compared with healthy samples using limma (linear models for microarray). Gene functional interaction networks were analyzed with Cytoscape and ReactomeFIViz...
April 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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/29666007/mutation-analysis-of-therapy-related-myeloid-neoplasms
#3
Takahiro Nishiyama, Yuichi Ishikawa, Naomi Kawashima, Akimi Akashi, Yoshiya Adachi, Hikaru Hattori, Yoko Ushijima, Hitoshi Kiyoi
We analyzed the genetic mutation status of 13 patients with therapy-related myeloid neoplasms (t-MN). Consistent with previous reports, t-MN cells preferentially acquired mutations in TP53 and epigenetic modifying genes, instead of mutations in tyrosine kinase and spliceosome genes. Furthermore, we compared the mutation status of three t-MN cells with each of the initial lymphoid malignant cells, and identified common mutations among t-MN and the initial malignant cells in two patients. In a patient who developed chronic myelomonocytic leukemia (CMML) after follicular lymphoma (FL), TET2 mutation was identified in both CMML and FL cells...
April 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29665143/identification-of-potential-tumor-educated-platelets-rna-biomarkers-in-non-small-cell-lung-cancer-by-integrated-bioinformatical-analysis
#4
Linlin Xue, Li Xie, Xingguo Song, Xianrang Song
BACKGROUND: Platelets have emerged as key players in tumorigenesis and tumor progression. Tumor-educated platelet (TEP) RNA profile has the potential to diagnose non-small-cell lung cancer (NSCLC). The objective of this study was to identify potential TEP RNA biomarkers for the diagnosis of NSCLC and to explore the mechanisms in alternations of TEP RNA profile. METHODS: The RNA-seq datasets GSE68086 and GSE89843 were downloaded from Gene Expression Omnibus DataSets (GEO DataSets)...
April 17, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29650551/hnrnpa1-promotes-recognition-of-splice-site-decoys-by-u2af2-in-vivo
#5
Jonathan M Howard, Hai Lin, Andrew J Wallace, Garam Kim, Jolene M Draper, Maximilian Haeussler, Sol Katzman, Masoud Toloue, Yunlong Liu, Jeremy R Sanford
Alternative pre-mRNA splicing plays a major role in expanding the transcript output of human genes. This process is regulated, in part, by the interplay of trans -acting RNA binding proteins (RBPs) with myriad cis -regulatory elements scattered throughout pre-mRNAs. These molecular recognition events are critical for defining the protein-coding sequences (exons) within pre-mRNAs and directing spliceosome assembly on noncoding regions (introns). One of the earliest events in this process is recognition of the 3' splice site (3'ss) by U2 small nuclear RNA auxiliary factor 2 (U2AF2)...
April 12, 2018: Genome Research
https://www.readbyqxmd.com/read/29643205/in-vitro-iclip-based-modeling-uncovers-how-the-splicing-factor-u2af2-relies-on-regulation-by-cofactors
#6
F X Reymond Sutandy, Stefanie Ebersberger, Lu Huang, Anke Busch, Maximilian Bach, Hyun-Seo Kang, Jörg Fallmann, Daniel Maticzka, Rolf Backofen, Peter F Stadler, Kathi Zarnack, Michael Sattler, Stefan Legewie, Julian König
Alternative splicing generates distinct mRNA isoforms and is crucial for proteome diversity in eukaryotes. The RNA-binding protein (RBP) U2AF2 is central to splicing decisions, as it recognizes 3' splice sites and recruits the spliceosome. We establish "in vitro iCLIP" experiments, in which recombinant RBPs are incubated with long transcripts, to study how U2AF2 recognizes RNA sequences and how this is modulated by trans -acting RBPs. We measure U2AF2 affinities at hundreds of binding sites and compare in vitro and in vivo binding landscapes by mathematical modeling...
April 11, 2018: Genome Research
https://www.readbyqxmd.com/read/29642843/interest-intron-exon-retention-estimator
#7
Ali Oghabian, Dario Greco, Mikko J Frilander
BACKGROUND: In-depth study of the intron retention levels of transcripts provide insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally, detailed analysis of retained introns can link these introns to post-transcriptional regulation or identify aberrant splicing events in human diseases. RESULTS: We present IntEREst, Intron-Exon Retention Estimator, an R package that supports rigorous analysis of non-annotated intron retention events (in addition to the ones annotated by RefSeq or similar databases), and support intra-sample in addition to inter-sample comparisons...
April 11, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29628886/u1-snrnp-alteration-and-neuronal-cell-cycle-reentry-in-alzheimer-disease
#8
REVIEW
Bing Bai
The aberrancy of U1 small nuclear ribonucleoprotein (snRNP) complex and RNA splicing has been demonstrated in Alzheimer's disease (AD). Importantly, the U1 proteopathy is AD-specific, widespread and early-occurring, thus providing a very unique clue to the AD pathogenesis. The prominent feature of U1 histopathology is its nuclear depletion and redistribution in the neuronal cytoplasm. According to the preliminary data, the initial U1 cytoplasmic distribution pattern is similar to the subcellular translocation of the spliceosome in cells undergoing mitosis...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29627519/significant-upregulation-of-u1-and-u4-spliceosomal-snrnas-by-atp-nanoliposomes-explains-acceleration-of-wound-healing-due-to-increased-pre-mrna-processing-to-functional-mrna
#9
Girish J Kotwal, Michael D Martin, Sufan Chien
Delayed wound healing is one of the hallmarks of diabetic complications and certain autoimmune inflammatory diseases. Extensive wound healing studies in rabbits have indicated that the delivery of ATP encapsulated in unilamellar nanoliposomes causes rapid cell proliferation and fast tracks the wound healing process. In the current study, we explored the possible molecular mechanism underlying this response by comparing gene expression in cultured rabbit kidney cells treated with either ATP nanoliposomes (containing 1mgMg-ATP/ml formulation) or control nanoliposomes (containing 1 mg/ml unmetabolisable gamma-thio-ATP/ml formulation)...
April 5, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29617656/impaired-spermatogenesis-muscle-and-erythrocyte-function-in-u12-intron-splicing-defective-zrsr1-mutant-mice
#10
Keiko Horiuchi, Serafín Perez-Cerezales, Panagiotis Papasaikas, Priscila Ramos-Ibeas, Angela Patricia López-Cardona, Ricardo Laguna-Barraza, Noelia Fonseca Balvís, Eva Pericuesta, Raul Fernández-González, Benjamín Planells, Alberto Viera, Jose Angel Suja, Pablo Juan Ross, Francisco Alén, Laura Orio, Fernando Rodriguez de Fonseca, Belén Pintado, Juan Valcárcel, Alfonso Gutiérrez-Adán
The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes. To analyze ZRSR1 function and its precise role in RNA splicing, we generated ZRSR1 mutant mice containing truncating mutations within its RNA-recognition motif. Homozygous mutant mice exhibited severe defects in erythrocytes, muscle stretch, and spermatogenesis, along with germ cell sloughing and apoptosis, ultimately leading to azoospermia and male sterility...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29610475/the-long-tail-of-oncogenic-drivers-in-prostate-cancer
#11
Joshua Armenia, Stephanie A M Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K Chatila, Debyani Chakravarty, G Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M Bielski, Alexander V Penson, Charlotte Tolonen, Franklin W Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A Garraway, Francesca Demichelis, Philip W Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S Taylor, Howard I Scher, Peter S Nelson, Johann S de Bono, Mark A Rubin, Charles L Sawyers, Arul M Chinnaiyan, Nikolaus Schultz, Eliezer M Van Allen
Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway...
April 2, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29606099/unexpected-conservation-of-the-rna-splicing-apparatus-in-the-highly-streamlined-genome-of-galdieria-sulphuraria
#12
Huan Qiu, Alessandro W Rossoni, Andreas P M Weber, Hwan Su Yoon, Debashish Bhattacharya
BACKGROUND: Genome reduction in intracellular pathogens and endosymbionts is usually compensated by reliance on the host for energy and nutrients. Free-living taxa with reduced genomes must however evolve strategies for generating functional diversity to support their independent lifestyles. An emerging model for the latter case is the Rhodophyta (red algae) that comprises an ecologically widely distributed, species-rich phylum. Red algae have undergone multiple phases of significant genome reduction, including extremophilic unicellular taxa with limited nuclear gene inventories that must cope with hot, highly acidic environments...
April 2, 2018: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/29602264/the-cyclin-dependent-kinase-g-group-defines-a-thermo-sensitive-alternative-splicing-circuit-modulating-the-expression-of-arabidopsis-atu2af65a
#13
Nicola Cavallari, Candida Nibau, Armin Fuchs, Despoina Dadarou, Andrea Barta, John H Doonan
The ability to adapt growth and development to temperature variations is crucial to generate plant varieties resilient to predicted temperature changes. However, the mechanisms underlying plant response to progressive increases in temperature have just started to be elucidated. Here, we report that the Cyclin-dependent Kinase G1 (CDKG1) is a central element in a thermo-sensitive mRNA splicing cascade that transduces changes in ambient temperature into differential expression of the fundamental spliceosome component, ATU2AF65A...
March 30, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29593291/structural-insights-into-the-rna-methyltransferase-domain-of-mettl16
#14
Agnieszka Ruszkowska, Milosz Ruszkowski, Zbigniew Dauter, Jessica A Brown
N6 -methyladenosine (m6 A) is an abundant modification in messenger RNA and noncoding RNAs that affects RNA metabolism. Methyltransferase-like protein 16 (METTL16) is a recently confirmed m6 A RNA methyltransferase that methylates U6 spliceosomal RNA and interacts with the 3'-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Here, we present two X-ray crystal structures of the N-terminal methyltransferase domain (residues 1-291) of human METTL16 (METTL16_291): an apo structure at 1...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29588184/the-matrices-and-constraints-of-gt-ag-splice-sites-of-more-than-1000-species-lineages
#15
Hai Nguyen, Urmi Das, Benjamin Wang, Jiuyong Xie
To provide a resource for the splice sites (SS) of different species, we calculated the matrices of nucleotide compositions of about 38 million splice sites from >1000 species/lineages. The matrices are enriched of aGGTAAGT (5'SS) or (Y)6 N(C/t)AG(g/a)t (3'SS) overall; however, they are quite diverse among hundreds of species. The diverse matrices remain prominent even under sequence selection pressures, suggesting the existence of diverse constraints as well as U snRNAs and other spliceosomal factors and/or their interactions with the splice sites...
March 24, 2018: Gene
https://www.readbyqxmd.com/read/29563537/mutation-patterns-identify-adult-patients-with-de-novo-acute-myeloid-leukemia-aged-60-years-or-older-who-respond-favorably-to-standard-chemotherapy-an-analysis-of-alliance-studies
#16
Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, James S Blachly, Christopher J Walker, Deedra Nicolet, Shelley Orwick, Sophia E Maharry, Andrew J Carroll, Richard M Stone, Albert de la Chapelle, Eunice S Wang, Jonathan E Kolitz, Bayard L Powell, John C Byrd, Clara D Bloomfield
Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS)...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29558158/interactome-analysis-of-ns1-protein-encoded-by-influenza-a-h7n9-virus-reveals-an-inhibitory-role-of-ns1-in-host-mrna-maturation
#17
Rei-Lin Kuo, Chi-Jene Chen, Ee-Hong Tam, Chung-Guei Huang, Li-Hsin Li, Zong-Hua Li, Pei-Chia Su, Hao-Ping Liu, Chih-Ching Wu
Influenza A virus infections can result in severe respiratory diseases. The H7N9 subtype of avian influenza A virus has been transmitted to humans and caused severe disease and death. Nonstructural protein 1 (NS1) of influenza A virus is a virulence determinant during viral infection. To elucidate the functions of the NS1 encoded by influenza A H7N9 virus (H7N9 NS1), interaction partners of H7N9 NS1 in human cells were identified with immunoprecipitation followed by SDS-PAGE coupled with liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)...
March 20, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29551686/histone-and-rna-binding-protein-interaction-creates-crosstalk-network-for-regulation-of-alternative-splicing
#18
Yong-Eun Kim, Chungoo Park, Kyoon Eon Kim, Kee K Kim
Alternative splicing is an essential process in eukaryotes, as it increases the complexity of gene expression by generating multiple proteins from a single pre-mRNA. However, information on the regulatory mechanisms for alternative splicing is lacking, because splicing occurs over a short period via the transient interactions of proteins within functional complexes of the spliceosome. Here, we investigated in detail the molecular mechanisms connecting alternative splicing with epigenetic mechanisms. We identified interactions between histone proteins and splicing factors such as Rbfox2, Rbfox3, and splicing factor proline and glutamine rich protein (SFPQ) by in vivo crosslinking and immunoprecipitation...
March 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29545468/insight-into-genes-regulating-post-harvest-aflatoxin-contamination-of-tetraploid-peanut-from-transcriptional-profiling
#19
Walid Korani, Ye Chu, C Corley Holbrook, Peggy Ozias-Akins
Post-harvest aflatoxin contamination is a challenging issue that affects peanut quality. Aflatoxin is produced by fungi belonging to the Aspergilli group, and is known as an acutely toxic, carcinogenic and immune-suppressing class of mycotoxins. Evidence for several host genetic factors that may impact aflatoxin contamination has been reported, e.g. , genes for lipoxygenase (PnLOX1 and PnLOX2/PnLOX3 that showed either positive or negative regulation with Aspergillus infection), ROS, and WRKY (highly associated with or differentially expressed upon infection of maize with A...
March 15, 2018: Genetics
https://www.readbyqxmd.com/read/29534719/formation-of-chimeric-genes-with-essential-functions-at-the-origin-of-eukaryotes
#20
Raphaël Méheust, Debashish Bhattacharya, Jananan S Pathmanathan, James O McInerney, Philippe Lopez, Eric Bapteste
BACKGROUND: Eukaryotes evolved from the symbiotic association of at least two prokaryotic partners, and a good deal is known about the timings, mechanisms, and dynamics of these evolutionary steps. Recently, it was shown that a new class of nuclear genes, symbiogenetic genes (S-genes), was formed concomitant with endosymbiosis and the subsequent evolution of eukaryotic photosynthetic lineages. Understanding their origins and contributions to eukaryogenesis would provide insights into the ways in which cellular complexity has evolved...
March 13, 2018: BMC Biology
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