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https://www.readbyqxmd.com/read/29415469/circsmarca5-inhibits-migration-of-glioblastoma-multiforme-cells-by-regulating-a-molecular-axis-involving-splicing-factors-srsf1-srsf3-ptb
#1
Davide Barbagallo, Angela Caponnetto, Matilde Cirnigliaro, Duilia Brex, Cristina Barbagallo, Floriana D'Angeli, Antonio Morrone, Rosario Caltabiano, Giuseppe Maria Barbagallo, Marco Ragusa, Cinzia Di Pietro, Thomas Birkballe Hansen, Michele Purrello
Circular RNAs (circRNAs) have recently emerged as a new class of RNAs, highly enriched in the brain and very stable within cells, exosomes and body fluids. To analyze their involvement in glioblastoma multiforme (GBM) pathogenesis, we assayed the expression of twelve circRNAs, physiologically enriched in several regions of the brain, through real-time PCR in a cohort of fifty-six GBM patient biopsies and seven normal brain parenchymas. We focused on hsa_circ_0001445 (circSMARCA5): it was significantly downregulated in GBM biopsies as compared to normal brain tissues (p-value < 0...
February 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29394380/the-mechanisms-of-a-mammalian-splicing-enhancer
#2
Andrew M Jobbins, Linus F Reichenbach, Christian M Lucas, Andrew J Hudson, Glenn A Burley, Ian C Eperon
Exonic splicing enhancer (ESE) sequences are bound by serine & arginine-rich (SR) proteins, which in turn enhance the recruitment of splicing factors. It was inferred from measurements of splicing around twenty years ago that Drosophila doublesex ESEs are bound stably by SR proteins, and that the bound proteins interact directly but with low probability with their targets. However, it has not been possible with conventional methods to demonstrate whether mammalian ESEs behave likewise. Using single molecule multi-colour colocalization methods to study SRSF1-dependent ESEs, we have found that that the proportion of RNA molecules bound by SRSF1 increases with the number of ESE repeats, but only a single molecule of SRSF1 is bound...
January 31, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29335301/mobilization-of-a-splicing-factor-through-a-nuclear-kinase-kinase-complex
#3
Brandon E Aubol, Malik M Keshwani, Laurent Fattet, Joseph A Adams
The splicing of mRNA is dependent on serine-arginine (SR) proteins that are mobilized from membrane-free, nuclear speckles to the nucleoplasm by the Cdc2-like kinases (CLKs). This movement is critical for SR protein-dependent assembly of the macromolecular spliceosome. Although CLK1 facilitates such trafficking through the phosphorylation of serine-proline dipeptides in the prototype SR protein SRSF1, an unrelated enzyme known as SR protein kinase 1 (SRPK1) performs the same function but does not efficiently modify these dipeptides in SRSF1...
January 15, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29331391/microrna-mediated-regulation-of-splicing-factors-srsf1-srsf2-and-hnrnp-a1-in-context-of-their-alternatively-spliced-3-utrs
#4
Elżbieta Sokół, Hanna Kędzierska, Alicja Czubaty, Beata Rybicka, Katarzyna Rodzik, Zbigniew Tański, Joanna Bogusławska, Agnieszka Piekiełko-Witkowska
SRSF1, SRSF2 and hnRNP A1 are splicing factors that regulate the expression of oncogenes and tumor suppressors. SRSF1 and SRSF2 contribute to the carcinogenesis in the kidney. Despite their importance, the mechanisms regulating their expression in cancer are not entirely understood. Here, we investigated the microRNA-mediated regulation of SRSF1, SRSF2 and hnRNP A1 in renal cancer. The expression of microRNAs predicted to target SRSF1, SRSF2 and hnRNP A1 was disturbed in renal tumors compared with controls...
January 10, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29288986/expression-profile-of-three-splicing-factors-in-pleural-cells-based-on-the-underlying-etiology-and-its-clinical-values-in-patients-with-pleural-effusion
#5
A-Lum Han, Hak-Ryul Kim, Keum-Ha Choi, Jae-Won Ryu, Ki-Eun Hwang, Hong-Seob So, Min-Cheol Park, Mengyu Zhu, Yuya Huang, Young-Jin Lee, Do-Sim Park
Splicing factors (SFs) are involved in oncogenesis or immune modulation, the common underlying processes giving rise to pleural effusion (PE). The expression profiles of three SFs (HNRNPA1, SRSF1, and SRSF3) and their clinical values have never been assessed in PE. The three SFs (in pellets of PE) and conventional tumor markers were analyzed using PE samples in patients with PE (N = 336). The sum of higher-molecular weight (Mw) forms of HNRNPA1 (Sum-HMws-HNRNPA1) and SRSF1 (Sum-HMws-SRSF1) and SRSF3 levels were upregulated in malignant PE (MPE) compared to benign PE (BPE); they were highest in cytology-positive MPE, followed by tuberculous PE and parapneumonic PE...
December 27, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29262322/srsf1-prevents-dna-damage-and-promotes-tumorigenesis-through-regulation-of-dbf4b-pre-mrna-splicing
#6
Linlin Chen, Chunling Luo, Lei Shen, Yuguo Liu, Qianqian Wang, Chang Zhang, Ruochen Guo, Yanan Zhang, Zhiqin Xie, Ning Wei, Wenwu Wu, Jun Han, Ying Feng
Dysregulated alternative splicing events have been implicated in many types of cancer, but the underlying molecular mechanisms remain unclear. Here, we observe that the splicing factor SRSF1 regulates DBF4B exon6 splicing by specifically binding and promoting its inclusion. Knockdown of the exon6-containing isoform (DBF4B-FL) significantly inhibits the tumorigenic potential of colon cancer cells in vitro and in mice, and SRSF1 inactivation phenocopies DBF4B-FL depletion. DBF4B-FL and SRSF1 are required for cancer cell proliferation and for the maintenance of genomic stability...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29233683/caspase-mediated-cleavage-of-x-ray-repair-cross-complementing-group-4-promotes-apoptosis-by-enhancing-nuclear-translocation-of-caspase-activated-dnase
#7
Yumi Sunatani, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, Tadashi Matsui, Ryo Sakasai, Mitsumasa Hashimoto, Yasuhito Ishigaki, Yoshihisa Matsumoto, Kuniyoshi Iwabuchi
X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation...
December 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29156724/lncrna-pvt1-and-its-splicing-variant-function-as-competing-endogenous-rna-to-regulate-clear-cell-renal-cell-carcinoma-progression
#8
Tao Yang, Hui Zhou, Peijun Liu, Libin Yan, Weimin Yao, Ke Chen, Jin Zeng, Heng Li, Junhui Hu, Hua Xu, Zhangqun Ye
Long non-coding RNAs (lncRNAs) exert critical regulatory roles in the development and progression of several cancers. Plasmacytoma variant translocation 1 (PVT1), an lncRNA, was shown to be upregulated in clear cell renal cell carcinoma (ccRCC) in our study, while Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival (OS) and disease free survival (DFS) in ccRCC patients. In vitro experiments revealed that PVT1 promoted renal cancer cell proliferation, migration, and invasion, while in vivo studies confirmed its oncogenic roles in ccRCC...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133510/single-cell-immuno-laser-microdissection-coupled-to-label-free-proteomics-to-reveal-the-proteotypes-of-human-brain-cells-after-ischemia
#9
Teresa García-Berrocoso, Víctor Llombart, Laura Colàs-Campàs, Alexandre Hainard, Virginie Licker, Anna Penalba, Laura Ramiro, Alba Simats, Alejandro Bustamante, Elena Martínez-Saez, Francesc Canals, Jean-Charles Sanchez, Joan Montaner
Cerebral ischemia entails rapid tissue damage in the affected brain area causing devastating neurological dysfunction. How each component of the neurovascular unit contributes or responds to the ischemic insult in the context of the human brain has not been solved yet. Thus, the analysis of the proteome is a straightforward approach to unraveling these cell proteotypes.In this study, post-mortem brain slices from ischemic stroke patients were obtained corresponding to infarcted (IC) and contralateral (CL) areas...
November 13, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29120871/a-srsf1-self-binding-mechanism-restrains-mir505-3p-from-inhibiting-proliferation-of-neural-tumor-cell-lines
#10
Kan Yang, Li Tong, Kai Li, Yuxun Zhou, Junhua Xiao
Srsf1 has currently been demonstrated to be an oncogene that is precisely autoregulated for normal physiology. Although Mir505-3p has been reported as one of the regulatory miRNAs of Srsf1 in mouse embryonic fibroblast (MEF), the inhibitory effect of Mir505-3p on Srsf1 is poorly described in neural tumors. Whether SRSF1 autoregulation interferes with miRNA targeting on the Srsf1 transcript is unclear. In this work, we screened out one target site, out of three potential target sites on 3' UTR of Srsf1 transcript, that was required for Mir505-3p targeting...
November 8, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29113173/bioinformatics-analysis-of-srsf1-controlled-gene-networks-in-colorectal-cancer
#11
Junxiu Sheng, Jinyao Zhao, Qiuhong Xu, Linlin Wang, Wenjing Zhang, Yang Zhang
Colorectal cancer is the third most common type of cancer and the fourth leading cause of cancer-associated mortality worldwide. Serine/arginine-rich splicing factor 1 (SRSF1) is a well-characterized oncogenic factor that promotes tumorigenesis by controlling a number of alternative splicing events. However, there is limited network analysis, from a global aspect, to study the effect of SRSF1 on colorectal cancer. In the present study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of available gene regulation data from The Cancer Genome Atlas database revealed the enriched functions and signaling pathways of SRSF1...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29100409/overcoming-imatinib-resistance-conferred-by-the-bim-deletion-polymorphism-in-chronic-myeloid-leukemia-with-splice-switching-antisense-oligonucleotides
#12
Jun Liu, Malini Bhadra, Joanna Rajeswary Sinnakannu, Wan Lin Yue, Cheryl Weiqi Tan, Frank Rigo, S Tiong Ong, Xavier Roca
Many tyrosine kinase-driven cancers, including chronic myeloid leukemia (CML), are characterized by high response rates to specific tyrosine kinase inhibitors (TKIs) like imatinib. In East Asians, primary imatinib resistance is caused by a deletion polymorphism in Intron 2 of the BIM gene, whose product is required for TKI-induced apoptosis. The deletion biases BIM splicing from exon 4 to exon 3, generating splice isoforms lacking the exon 4-encoded pro-apoptotic BH3 domain, which impairs the ability of TKIs to induce apoptosis...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28990926/irak2-directs-stimulus-dependent-nuclear-export-of-inflammatory-mrnas
#13
Hao Zhou, Katarzyna Bulek, Xiao Li, Tomasz Herjan, Minjia Yu, Wen Qian, Han Wang, Gao Zhou, Xing Chen, Hui Yang, Lingzi Hong, Junjie Zhao, Luke Qin, Koichi Fukuda, Annette Flotho, Ji Gao, Ashok Dongre, Julie A Carman, Zizhen Kang, Bing Su, Timothy S Kern, Jonathan D Smith, Thomas A Hamilton, Frauke Melchior, Paul L Fox, Xiaoxia Li
Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation...
October 9, 2017: ELife
https://www.readbyqxmd.com/read/28990563/-ribosomes-synthesis-at-the-heart-of-cell-proliferation
#14
Clément Madru, Nicolas Leulliot, Simon Lebaron
Ribosomes are central to gene expression. Their assembly is a complex and an energy consuming process. Many controls exist to make it possible a fine-tuning of ribosome production adapted to cell needs. In this review, we describe recent advances in the characterisation of the links occurring between ribosome synthesis and cell proliferation control. Defects in ribosome biogenesis directly impede cellular cycle and slow-down proliferation. Among the different factors involved, we could define the 5S particle, a ribosome sub-complex, as a key-regulator of p53 and other tumour suppressors such as pRB...
June 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28886419/mutation-in-an-exonic-splicing-enhancer-site-causing-chronic-granulomatous-disease
#15
Martin de Boer, Karin van Leeuwen, Judy Geissler, Bernd H Belohradsky, Taco W Kuijpers, Dirk Roos
In a male patient suffering from X-linked chronic granulomatous disease (CGD) we found a c.389G>T mutation in exon 5 of the CYBB gene. We have analyzed why 95% of the transcripts of this gene lacked exon 5, leading to a frameshift and premature termination codon. The mutation was located in a region comprising three putative exonic splicing enhancer binding sites, for SRSF1, SRFS2 and SRFS6, according to the ESEfinder Tool (http://rulai.cshl.edu/cgi-bin/tools/ESE3/esefinder.cgi). With the Analyser Splice Tool we calculated the probability of skipping of exon 5 in CYBB mRNA, and by means of Sroogle the number of putative binding motifs for splicing enhancer and splicing silencer proteins (http://astlab...
July 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28874828/srsf1-suppresses-selection-of-intron-distal-5-splice-site-of-dok7-intron-4-to-generate-functional-full-length-dok-7-protein
#16
Khalid Bin Ahsan, Akio Masuda, Mohammad Alinoor Rahman, Jun-Ichi Takeda, Mohammad Nazim, Bisei Ohkawara, Mikako Ito, Kinji Ohno
Dok-7 is a non-catalytic adaptor protein that facilitates agrin-induced clustering of acetylcholine receptors (AChR) at the neuromuscular junction. Alternative selection of 5' splice sites (SSs) of DOK7 intron 4 generates canonical and frame-shifted transcripts. We found that the canonical full-length Dok-7 enhanced AChR clustering, whereas the truncated Dok-7 did not. We identified a splicing cis-element close to the 3' end of exon 4 by block-scanning mutagenesis. RNA affinity purification and mass spectrometry revealed that SRSF1 binds to the cis-element...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843252/overexpression-of-antiangiogenic-vascular-endothelial-growth-factor-isoform-and-splicing-regulatory-factors-in-oral-laryngeal-and-pharyngeal-squamous-cell-carcinomas
#17
Patrícia Matos Biselli-Chicote, Joice Matos Biselli, Bianca R Cunha, Rodrigo Castro, José Victor Maniglia, Dalísio de Santi Neto, Eloiza Helena Tajara, José Franscisco de Góis Filho, Erica Erina Fukuyama, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo
Background: Overexpression of proangiogenic vascular endothelial growth factor A family VEGFAxxx is associated with tumor growth and metastasis. The role of the alternatively spliced antiangiogenic family VEGFAxxxb is poorly investigated in head and neck squamous cell carcinomas (HNSCCs). The antiangiogenic isoform binds to bevacizumab and its expression level could influence the treatment response and progression-free survival. In this study, the relative expression of VEGFAxxx and VEGFA165b isoforms and splicing regulatory factors genes was investigated in a series of HNSCCs...
August 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28800142/alcohol-mediated-missplicing-of-mcl-1-pre-mrna-is-involved-in-neurotoxicity
#18
Rahsan Sariyer, Francesca I De-Simone, Martina Donadoni, Jan B Hoek, Sulie L Chang, Ilker Kudret Sariyer
BACKGROUND: Heavy and chronic ethanol (EtOH) exposure can cause significant structural and functional damage to the adult brain. The most devastating consequence of EtOH exposure is the neurotoxicity associated with the depletion of neurons. Regulation of splice variants in the brain can modulate protein functions, which may ultimately affect behaviors associated with alcohol dependence and EtOH-mediated neurotoxicity. As alcohol consumption is associated with neurotoxicity, it is possible that altered splicing of survival and pro-survival factors during the development of alcoholism may contribute to the neurotoxicity...
October 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28799539/srsf1-promotes-vascular-smooth-muscle-cell-proliferation-through-a-%C3%AE-133p53-egr1-klf5-pathway
#19
Ning Xie, Min Chen, Rilei Dai, Yan Zhang, Hanqing Zhao, Zhiming Song, Lufeng Zhang, Zhenyan Li, Yuanqing Feng, Hua Gao, Li Wang, Ting Zhang, Rui-Ping Xiao, Jianxin Wu, Chun-Mei Cao
Though vascular smooth muscle cell (VSMC) proliferation underlies all cardiovascular hyperplastic disorders, our understanding of the molecular mechanisms responsible for this cellular process is still incomplete. Here we report that SRSF1 (serine/arginine-rich splicing factor 1), an essential splicing factor, promotes VSMC proliferation and injury-induced neointima formation. Vascular injury in vivo and proliferative stimuli in vitro stimulate SRSF1 expression. Mice lacking SRSF1 specifically in SMCs develop less intimal thickening after wire injury...
August 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28747380/identification-of-differentially-expressed-splice-variants-by-the-proteogenomic-pipeline-splicify
#20
Malgorzata A Komor, Thang V Pham, Annemieke C Hiemstra, Sander R Piersma, Anne S Bolijn, Tim Schelfhorst, Pien M Delis-van Diemen, Marianne Tijssen, Robert P Sebra, Meredith Ashby, Gerrit A Meijer, Connie R Jimenez, Remond J A Fijneman
Proteogenomics, i.e. comprehensive integration of genomics and proteomics data, is a powerful approach identifying novel protein biomarkers. This is especially the case for proteins that differ structurally between disease and control conditions. As tumor development is associated with aberrant splicing, we focus on this rich source of cancer specific biomarkers. To this end, we developed a proteogenomic pipeline, Splicify, which can detect differentially expressed protein isoforms. Splicify is based on integrating RNA massive parallel sequencing data and tandem mass spectrometry proteomics data to identify protein isoforms resulting from differential splicing between two conditions...
October 2017: Molecular & Cellular Proteomics: MCP
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