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https://www.readbyqxmd.com/read/28637317/evidence-of-nuclei-encoded-spliceosome-mediating-splicing-of-mitochondrial-rna
#1
Roberto H Herai, Priscilla D Negraes, Alysson R Muotri
No abstract text is available yet for this article.
July 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28637241/the-chromatin-remodeling-complex-swi-snf-regulates-splicing-of-meiotic-transcripts-in-saccharomyces-cerevisiae
#2
Srivats Venkataramanan, Stephen Douglass, Anoop R Galivanche, Tracy L Johnson
Despite its relatively streamlined genome, there are important examples of regulated RNA splicing in Saccharomyces cerevisiae, such as splicing of meiotic transcripts. Like other eukaryotes, S. cerevisiae undergoes a dramatic reprogramming of gene expression during meiosis, including regulated splicing of a number of crucial meiosis-specific RNAs. Splicing of a subset of these is dependent upon the splicing activator Mer1. Here we show a crucial role for the chromatin remodeler Swi/Snf in regulation of splicing of meiotic genes and find that the complex affects meiotic splicing in two ways...
May 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28629821/glycogen-reduction-in-myotubes-of-late-onset-pompe-disease-patients-using-antisense-technology
#3
Elisa Goina, Paolo Peruzzo, Bruno Bembi, Andrea Dardis, Emanuele Buratti
Glycogen storage disease type II (GSDII) is a lysosomal disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme, leading to the accumulation of glycogen within the lysosomes. The disease has been classified in infantile and late-onset forms. Most late-onset patients share a splicing mutation c.-32-13T > G in intron 1 of the GAA gene that prevents efficient recognition of exon 2 by the spliceosome. In this study, we have mapped the splicing silencers of GAA exon 2 and developed antisense morpholino oligonucleotides (AMOs) to inhibit those regions and rescue normal splicing in the presence of the c...
June 16, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28628606/splicing-stimulates-sirna-formation-at-drosophila-dna-double-strand-breaks
#4
Karin Merk, Marco Breinig, Romy Böttcher, Stefan Krebs, Helmut Blum, Michael Boutros, Klaus Förstemann
DNA double-strand breaks trigger the production of locus-derived siRNAs in fruit flies, human cells and plants. At least in flies, their biogenesis depends on active transcription running towards the break. Since siRNAs derive from a double-stranded RNA precursor, a major question is how broken DNA ends can generate matching sense and antisense transcripts. We performed a genome-wide RNAi-screen in cultured Drosophila cells, which revealed that in addition to DNA repair factors, many spliceosome components are required for efficient siRNA generation...
June 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28622506/dynamic-rna-modifications-in-gene-expression-regulation
#5
REVIEW
Ian A Roundtree, Molly E Evans, Tao Pan, Chuan He
Over 100 types of chemical modifications have been identified in cellular RNAs. While the 5' cap modification and the poly(A) tail of eukaryotic mRNA play key roles in regulation, internal modifications are gaining attention for their roles in mRNA metabolism. The most abundant internal mRNA modification is N(6)-methyladenosine (m(6)A), and identification of proteins that install, recognize, and remove this and other marks have revealed roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28621911/different-roles-of-cd4-cd8-and-%C3%AE-%C3%AE-t-lymphocytes-in-naive-and-vaccinated-chickens-during-s-enteritidis-infection
#6
Zuzana Sekelova, Ondrej Polansky, Hana Stepanova, Radek Fedr, Marcela Faldynova, Ivan Rychlik, Lenka Vlasatikova
Lymphocytes represent the key antigen-specific leukocyte subpopulation. Despite their importance in mounting an immune response, an unbiased description of proteins expressed by chicken lymphocytes has not been presented. In this study we therefore intravenously infected chickens with Salmonella Enteritidis, sorted CD4, CD8 and γδ T-lymphocytes from the spleen by flow cytometry and determined the proteome of each population by LC-MS/MS. CD4 T-lymphocyte characteristic proteins included ubiquitin SUMO-like domain and BAR domain containing proteins...
June 16, 2017: Proteomics
https://www.readbyqxmd.com/read/28615231/single-nucleotide-polymorphism-leading-to-false-allelic-fraction-by-droplet-digital-pcr
#7
Eric S Christenson, William B Dalton, David Chu, Ian Waters, Karen Cravero, Daniel J Zabransky, Amy DeZern, Ben Ho Park
BACKGROUND: Molecular-based diagnostics have great utility for cancer detection. We have used droplet digital PCR (ddPCR) as a platform for identifying mutations in circulating plasma tumor DNA (ptDNA). We present the unexpected finding of a spurious mutant allele fraction that was discovered to be artifactual because of the presence of a single-nucleotide polymorphism (SNP) in a patient sample. DESIGN AND METHODS: Probe and primer combinations for the K700 and V701 loci of the SF3B1 spliceosome gene were designed for ddPCR to identify the percentage of mutant and wild-type alleles...
June 14, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28614712/evidence-that-c9orf72-dipeptide-repeat-proteins-associate-with-u2-snrnp-to-cause-mis-splicing-in-als-ftd-patients
#8
Shanye Yin, Rodrigo Lopez-Gonzalez, Ryan C Kunz, Jaya Gangopadhyay, Carl Borufka, Steven P Gygi, Fen-Biao Gao, Robin Reed
Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR) proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR) and glycine-arginine (GR) toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP) as a major interactor of PR and GR peptides...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612854/fragile-x-mental-retardation-protein-recognizes-a-g-quadruplex-structure-within-the-survival-motor-neuron-domain-containing-1-mrna-5-utr
#9
Damian S McAninch, Ashley M Heinaman, Cara N Lang, Kathryn R Moss, Gary J Bassell, Mihaela Rita Mihailescu, Timothy L Evans
G quadruplex structures have been predicted by bioinformatics to form in the 5'- and 3'-untranslated regions (UTRs) of several thousand mature mRNAs and are believed to play a role in translation regulation. Elucidation of these roles has primarily been focused on the 3'-UTR, with limited focus on characterizing the G quadruplex structures and functions in the 5'-UTR. Investigation of the affinity and specificity of RNA binding proteins for 5'-UTR G quadruplexes and the resulting regulatory effects have also been limited...
June 14, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28612833/variant-in-the-x-chromosome-spliceosomal-gene-gpkow-causes-male-lethal-microcephaly-with-intrauterine-growth-restriction
#10
Renée Carroll, Raman Kumar, Marie Shaw, Jennie Slee, Vera M Kalscheuer, Mark A Corbett, Jozef Gecz
Congenital microcephaly, with or without additional developmental defects, is a heterogeneous disorder resulting from impaired brain development during early fetal life. The majority of causative genetic variants identified thus far are inherited in an autosomal recessive manner and impact key cellular pathways such as mitosis, DNA damage response and repair, apoptosis and splicing. Here, we report a novel donor splice site variant in the G-patch domain and KOW motifs (GPKOW) gene (NG_021310.2:g.6126G>A, NM_015698...
June 14, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28611215/genome-wide-crispr-screen-identifies-hnrnpl-as-a-prostate-cancer-dependency-regulating-rna-splicing
#11
Teng Fei, Yiwen Chen, Tengfei Xiao, Wei Li, Laura Cato, Peng Zhang, Maura B Cotter, Michaela Bowden, Rosina T Lis, Shuang G Zhao, Qiu Wu, Felix Y Feng, Massimo Loda, Housheng Hansen He, X Shirley Liu, Myles Brown
Alternative RNA splicing plays an important role in cancer. To determine which factors involved in RNA processing are essential in prostate cancer, we performed a genome-wide CRISPR/Cas9 knockout screen to identify the genes that are required for prostate cancer growth. Functional annotation defined a set of essential spliceosome and RNA binding protein (RBP) genes, including most notably heterogeneous nuclear ribonucleoprotein L (HNRNPL). We defined the HNRNPL-bound RNA landscape by RNA immunoprecipitation coupled with next-generation sequencing and linked these RBP-RNA interactions to changes in RNA processing...
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28600326/up-frameshift-protein-upf1-regulates-neurospora-crassa-circadian-and-diurnal-growth-rhythms
#12
Yilan Wu, Yin Zhang, Yunpeng Sun, Jiali Yu, Peiliang Wang, Huan Ma, Shijunyin Chen, Lizhen Ma, Dongyang Zhang, Qun He, Jinhu Guo
Nonsense-mediated RNA decay (NMD) is a crucial post-transcriptional regulatory mechanism that recognizes and eliminates aberrantly processed transcripts, and mediates the expression of normal gene transcripts. In this study, we report that in the filamentous fungus Neurospora crassa, the NMD factors play a conserved role in regulating the surveillance of NMD targets including PTC-containing transcripts and normal transcripts. The circadian rhythms in all of the upf1-3 knockout strains, which are principle NMD factors, were aberrant...
June 9, 2017: Genetics
https://www.readbyqxmd.com/read/28596291/ddx54-regulates-transcriptome-dynamics-during-dna-damage-response
#13
Miha Milek, Koshi Imami, Neelanjan Mukherjee, Francesca De Bortoli, Ulrike Zinnall, Orsalia Hazapis, Christian Trahan, Marlene Oeffinger, Florian Heyd, Uwe Ohler, Matthias Selbach, Markus Landthaler
The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of posttranscriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing radiation (IR). Interestingly, more than 260 proteins including many nucleolar proteins showed increased binding to poly(A) RNA in IR-exposed cells...
June 8, 2017: Genome Research
https://www.readbyqxmd.com/read/28595329/a-mechanism-for-a-single-nucleotide-intron-shift
#14
Erzsébet Fekete, Michel Flipphi, Norbert Ág, Napsugár Kavalecz, Gustavo Cerqueira, Claudio Scazzocchio, Levente Karaffa
Spliceosomal introns can occupy nearby rather than identical positions in orthologous genes (intron sliding or shifting). Stwintrons are complex intervening sequences, where an 'internal' intron interrupts one of the sequences essential for splicing, generating after its excision, a newly formed canonical intron defined as 'external'. In one experimentally demonstrated configuration, two alternatively excised internal introns, overlapping by one G, disrupt respectively the donor and the acceptor sequence of an external intron, leading to mRNAs encoding identical proteins...
June 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28595116/the-unique-spliceosome-signature-of-human-pluripotent-stem-cells-is-mediated-by-snrpa1-snrpd1-and-pnn
#15
Young-Dae Kim, Jungwoon Lee, Han-Seop Kim, Mi-Ok Lee, Mi-Young Son, Chae Hwa Yoo, Jung-Kyun Choi, Sang Chul Lee, Yee Sook Cho
Spliceosomes are the core host of pre-mRNA splicing, allowing multiple protein isoforms to be produced from a single gene. Herein, we reveal that spliceosomes are more abundant in human pluripotent stem cells (hPSs), including human embryonic stem cells (hESs) and human induced pluripotent stem cells (hiPSs), than non-hPSs, and their presence is associated with high transcriptional activity. Supportively, spliceosomal components involved in the catalytically active pre-mRNA splicing step were mainly co-localized with hPS spliceosomes...
May 30, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28592875/splice-variants-as-novel-targets-in-pancreatic-ductal-adenocarcinoma
#16
Jun Wang, Laurent Dumartin, Andrea Mafficini, Pinar Ulug, Ajanthah Sangaralingam, Namaa Audi Alamiry, Tomasz P Radon, Roberto Salvia, Rita T Lawlor, Nicholas R Lemoine, Aldo Scarpa, Claude Chelala, Tatjana Crnogorac-Jurcevic
Despite a wealth of genomic information, a comprehensive alternative splicing (AS) analysis of pancreatic ductal adenocarcinoma (PDAC) has not been performed yet. In the present study, we assessed whole exome-based transcriptome and AS profiles of 43 pancreas tissues using Affymetrix exon array. The AS analysis of PDAC indicated on average two AS probe-sets (ranging from 1-28) in 1,354 significantly identified protein-coding genes, with skipped exon and alternative first exon being the most frequently utilised...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586478/autoregulation-of-rbm10-and-cross-regulation-of-rbm10-rbm5-via-alternative-splicing-coupled-nonsense-mediated-decay
#17
Yue Sun, Yufang Bao, Wenjian Han, Fan Song, Xianfeng Shen, Jiawei Zhao, Ji Zuo, David Saffen, Wei Chen, Zefeng Wang, Xintian You, Yongbo Wang
Mutations in the spliceosomal RNA binding protein RBM10 cause TARP syndrome and are frequently observed in lung adenocarcinoma (LUAD). We have previously shown that RBM10 enhances exon skipping of its target genes, including its paralog RBM5. Here, we report that RBM10 negatively regulates its own mRNA and protein expression and that of RBM5 by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). Through computational analysis and experimental validation, we identified RBM10-promoted skipping of exon 6 or 12 in RBM10 and exon 6 or 16 in RBM5 as the underlying AS-NMD events...
June 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28586220/discovery-of-allosteric-inhibitors-targeting-the-spliceosomal-rna-helicase-brr2
#18
Misa Iwatani-Yoshihara, Masahiro Ito, Michael G Klein, Takeshi Yamamoto, Kazuko Yonemori, Toshio Tanaka, Masanori Miwa, Daisuke Morishita, Satoshi Endo, Richard Tjhen, Ling Qin, Atsushi Nakanishi, Hironobu Maezaki, Tomohiro Kawamoto
Brr2 is an RNA helicase belonging to the Ski2-like subfamily, and an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation. An HTS campaign using an RNA-dependent ATPase assay and initial SAR study identified two different Brr2 inhibitors, 3 and 12. Co-crystal structures revealed 3 binds to an unexpected allosteric site between the C-terminal and the N-terminal helicase cassettes, while 12 binds an RNA-binding site inside the N-terminal cassette...
June 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28574823/integrated-transcriptomic-analysis-of-distance-related-field-cancerization-in-rectal-cancer-patients
#19
Honglin Guo, Weigen Zeng, Lin Feng, Xuexin Yu, Ping Li, Kaitai Zhang, Zhixiang Zhou, Shujun Cheng
Field cancerization (FC) occurs in various epithelial carcinomas, including colorectal cancer, which indicates that the molecular events in carcinogenesis might occur in normal tissues extending from tumors. However, the transcriptomic characteristics of FC in colorectal cancer (CRC) remain largely unexplored. To investigate the changes in gene expression associated with proximity to the tumor, we analyzed the global gene expression profiles of cancer tissues and histologically normal tissues taken at various distances from the tumor (1 cm, 5 cm and the proximal end of the resected sample) from 32 rectal cancer patients...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572631/understanding-the-mechanisms-of-dormancy-in-an-invasive-alien-sycamore-lace-bug-corythucha-ciliata-through-transcript-and-metabolite-profiling
#20
Feng-Qi Li, Ning-Ning Fu, Cheng Qu, Ran Wang, Yi-Hua Xu, Chen Luo
The sycamore lace bug, Corythucha ciliata, is a pest of sycamore trees. In China, it is found in the most northern border where it has been known to become dormant during harsh winters. But the molecular and metabolic basis for dormancy in this insect is still unknown. In this study, we analyzed the transcript and metabolite profiles of this bug to identify key genes and metabolites that are significantly regulated during dormancy in adult females and males. In total, 149 differentially expressed genes (DEGs) were significantly up-regulated and 337 DEGs were significantly down-regulated in dormant adults (both females and males)...
June 1, 2017: Scientific Reports
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