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https://www.readbyqxmd.com/read/29905030/decreased-expression-of-serine-arginine-rich-splicing-factor-1-in-t-cells-from-patients-with-active-systemic-lupus-erythematosus-accounts-for-reduced-expression-of-rasgrp1-and-dna-methyltransferase-1
#1
Michihiro Kono, Takashi Kurita, Shinsuke Yasuda, Michihito Kono, Yuichiro Fujieda, Toshiyuki Bohgaki, Takayuki Katsuyama, George C Tsokos, Vaishali R Moulton, Tatsuya Atsumi
OBJECTIVE: T cells from SLE patients have reduced protein levels of RasGRP1, a guanine nucleotide exchange factor for Ras, and increased transcript of alternatively spliced (AS) forms lacking exon 11. Serine/arginine-rich splicing factor 1 (SRSF1) binds pre-mRNA to regulate AS forms of several genes, including CD3ζ in SLE T cells. This study aimed to assess whether SRSF1 controls the expression of RasGRP1 in T cells from SLE patients. METHODS: We studied T cells from 45 SLE and 18 healthy subjects...
June 14, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29769310/tumor-associated-intronic-editing-of-hnrpll-generates-a-novel-splicing-variant-linked-to-cell-proliferation
#2
Yi-Tung Chen, Ian Yi-Feng Chang, Hsuan Liu, Chung-Pei Ma, Yu-Ping Kuo, Chieh-Tien Shih, Ying-Hsin Shih, Lin Kang, Bertrand Chin-Ming Tan
Processing of the eukaryotic transcriptome is a dynamic regulatory mechanism that confers genetic diversity, and splicing and A-to-I RNA editing are well-characterized examples of such processing. Growing evidence reveals the crosstalk between the splicing and RNA editing, but there is a paucity of substantial evidence for its mechanistic details and contribution in a physiological context. Here, our findings demonstrate that tumor-associated differential RNA editing, in conjunction with splicing machinery, regulates the expression of variants of HNRPLL, a gene encoding splicing factor...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29768215/mechanism-of-nonsense-mediated-mrna-decay-stimulation-by-splicing-factor-srsf1
#3
Isabel Aznarez, Tomoki T Nomakuchi, Jaclyn Tetenbaum-Novatt, Mohammad Alinoor Rahman, Oliver Fregoso, Holly Rees, Adrian R Krainer
The splicing factor SRSF1 promotes nonsense-mediated mRNA decay (NMD), a quality control mechanism that degrades mRNAs with premature termination codons (PTCs). Here we show that transcript-bound SRSF1 increases the binding of NMD factor UPF1 to mRNAs while in, or associated with, the nucleus, bypassing UPF2 recruitment and promoting NMD. SRSF1 promotes NMD when positioned downstream of a PTC, which resembles the mode of action of exon junction complex (EJC) and NMD factors. Moreover, splicing and/or EJC deposition increase the effect of SRSF1 on NMD...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29764005/identification-of-novel-functional-variants-of-sin3a-and-srsf1-among-somatic-variants-in-acute-myeloid-leukemia-patients
#4
Jae-Woong Min, Youngil Koh, Dae-Yoon Kim, Hyung-Lae Kim, Jeong A Han, Yu-Jin Jung, Sung-Soo Yoon, Sun Shim Choi
The advent of massively parallel sequencing, also called nextgeneration sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AMLrelated genes...
May 15, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29742442/rna-dna-hybrid-interactome-identifies-dxh9-as-a-molecular-player-in-transcriptional-termination-and-r-loop-associated-dna-damage
#5
Agnese Cristini, Matthias Groh, Maiken S Kristiansen, Natalia Gromak
R-loops comprise an RNA/DNA hybrid and displaced single-stranded DNA. They play important biological roles and are implicated in pathology. Even so, proteins recognizing these structures are largely undefined. Using affinity purification with the S9.6 antibody coupled to mass spectrometry, we defined the RNA/DNA hybrid interactome in HeLa cells. This consists of known R-loop-associated factors SRSF1, FACT, and Top1, and yet uncharacterized interactors, including helicases, RNA processing, DNA repair, and chromatin factors...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29741121/when-sumo-met-splicing
#6
Berta Pozzi, Pablo Mammi, Laureano Bragado, Luciana E Giono, Anabella Srebrow
Spliceosomal proteins have been revealed as SUMO conjugation targets. Moreover, we have reported that many of these are in a SUMO-conjugated form when bound to a pre-mRNA substrate during a splicing reaction. We demonstrated that SUMOylation of Prp3 (PRPF3), a component of the U4/U6 di-snRNP, is required for U4/U6•U5 tri-snRNP formation and/or recruitment to active spliceosomes. Expanding upon our previous results, we have shown that the splicing factor SRSF1 stimulates SUMO conjugation to several spliceosomal proteins...
May 9, 2018: RNA Biology
https://www.readbyqxmd.com/read/29676621/interleukin-17a-in-the-pathogenesis-of-lung-adenocarcinoma
#7
Zhen Lin, Christian Nguyen, Beibei Xu, Erik K Flemington, Gilbert F Morris
RATIONALE: Evidence has shown that inhaled lung carcinogens, such as tobacco smoke, silica, or asbestos, induce a T-helper cell type 17 inflammatory environment. Interleukin-17A (commonly and hereafter called IL-17) is the signature cytokine of T-helper cell type 17 inflammation. We have shown previously that IL-17 overexpression promotes growth of lung adenocarcinoma in transgenic mouse models. Our additional findings suggest that IL-17 suppresses the function of the p53 tumor suppressor protein in a mutant K-Ras-expressing lung tumor cell line...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29606096/hypoxia-leads-to-significant-changes-in-alternative-splicing-and-elevated-expression-of-clk-splice-factor-kinases-in-pc3-prostate-cancer-cells
#8
Elizabeth Bowler, Sean Porazinski, Simon Uzor, Philippe Thibault, Mathieu Durand, Elvy Lapointe, Kasper M A Rouschop, John Hancock, Ian Wilson, Michael Ladomery
BACKGROUND: Mounting evidence suggests that one of the ways that cells adapt to hypoxia is through alternative splicing. The aim of this study was firstly to examine the effect of hypoxia on the alternative splicing of cancer associated genes using the prostate cancer cell line PC3 as a model. Secondly, the effect of hypoxia on the expression of several regulators of splicing was examined. METHODS: PC3 cells were grown in 1% oxygen in a hypoxic chamber for 48 h, RNA extracted and sent for high throughput PCR analysis at the RNomics platform at the University of Sherbrooke, Canada...
April 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29558032/levels-of-egf-and-vegf-in-patients-with-primary-and-secondary-sj%C3%A3-gren-s-syndrome
#9
Katarzyna J Błochowiak, Dorota Trzybulska, Anna Olewicz-Gawlik, Jan J Sikora, Michalina Nowak-Gabryel, Jarosław Kocięcki, Henryk Witmanowski, Jerzy Sokalski
BACKGROUND: Aberrant angiogenesis plays a role in the pathogenesis of Sjögren's syndrome (SS). OBJECTIVES: The aim of this study was to compare the levels of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in stimulatory parotid saliva and in serum in healthy subjects (HS), patients with primary SS (pSS) and secondary SS (sSS) and to evaluate the expression of EGF, proangiogenic VEGF165 and antiangiogenic VEGF165 b mRNA isoforms. Additionally, we determined the salivary levels of serine/arginine splicing factor (SRSF1), which regulates VEGF165 and VEGF165 b expression...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29415469/circsmarca5-inhibits-migration-of-glioblastoma-multiforme-cells-by-regulating-a-molecular-axis-involving-splicing-factors-srsf1-srsf3-ptb
#10
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
#11
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...
March 16, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29335301/mobilization-of-a-splicing-factor-through-a-nuclear-kinase-kinase-complex
#12
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...
February 14, 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
#13
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...
February 15, 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
#14
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...
February 2018: Translational Oncology
https://www.readbyqxmd.com/read/29262322/srsf1-prevents-dna-damage-and-promotes-tumorigenesis-through-regulation-of-dbf4b-pre-mrna-splicing
#15
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
#16
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...
January 15, 2018: 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
#17
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
#18
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...
January 2018: 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
#19
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...
January 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29113173/bioinformatics-analysis-of-srsf1-controlled-gene-networks-in-colorectal-cancer
#20
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
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