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https://www.readbyqxmd.com/read/29235465/molecular-basis-of-differential-3-splice-site-sensitivity-to-anti-tumor-drugs-targeting-u2-snrnp
#1
Luisa Vigevani, André Gohr, Thomas Webb, Manuel Irimia, Juan Valcárcel
Several splicing-modulating compounds, including Sudemycins and Spliceostatin A, display anti-tumor properties. Combining transcriptome, bioinformatic and mutagenesis analyses, we delineate sequence determinants of the differential sensitivity of 3' splice sites to these drugs. Sequences 5' from the branch point (BP) region strongly influence drug sensitivity, with additional functional BPs reducing, and BP-like sequences allowing, drug responses. Drug-induced retained introns are typically shorter, displaying higher GC content and weaker polypyrimidine-tracts and BPs...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29219070/predicting-human-splicing-branchpoints-by-combining-sequence-derived-features-and-multi-label-learning-methods
#2
Wen Zhang, Xiaopeng Zhu, Yu Fu, Junko Tsuji, Zhiping Weng
BACKGROUND: Alternative splicing is the critical process in a single gene coding, which removes introns and joins exons, and splicing branchpoints are indicators for the alternative splicing. Wet experiments have identified a great number of human splicing branchpoints, but many branchpoints are still unknown. In order to guide wet experiments, we develop computational methods to predict human splicing branchpoints. RESULTS: Considering the fact that an intron may have multiple branchpoints, we transform the branchpoint prediction as the multi-label learning problem, and attempt to predict branchpoint sites from intron sequences...
December 1, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29187406/ptbp3-mediated-regulation-of-zeb1-mrna-stability-promotes-epithelial-mesenchymal-transition-in-breast-cancer
#3
Pingfu Hou, Lin Li, Fang Chen, Yansu Chen, Hui Liu, Jingjing Li, Jin Bai, Junnian Zheng
The RNA polypyrimidine tract binding protein PTBP3 is a little studied paralog of PTBP1 which has oncogenic properties. In this study, we demonstrate that PTBP3 induces epithelial-mesenchymal transition (EMT) in breast tumor cells and promotes their invasive growth and metastasis. Elevated expression of PTBP3 associated significantly with lymph node metastasis, advanced histology grade, TNM stage, and poor 5-year overall survival of patients. In human mammary epithelial cells, PTBP3 overexpression was sufficient to induce EMT and enhance cell migration, invasion, and cancer stem-like cell properties...
November 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/29186814/alternative-splicing-of-l-type-cav1-2-calcium-channels-implications-in-cardiovascular-diseases
#4
REVIEW
(no author information available yet)
L-type Cav1.2 calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alteration of Cav1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands Cav1.2 channel structures to modify function, pharmacological and biophysical property such as calcium/voltage-dependent inactivation (C/VDI), or to influence its post-translational modulation by interacting proteins such as Galectin-1...
November 24, 2017: Genes
https://www.readbyqxmd.com/read/29147905/transcriptional-regulation-of-dj-1
#5
Kazuko Takahashi-Niki, Takeshi Niki, Sanae M M Iguchi-Ariga, Hiroyoshi Ariga
DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29140550/lncrna-h19-interacts-with-polypyrimidine-tract-binding-protein-1-to-reprogram-hepatic-lipid-homeostasis
#6
Chune Liu, Zhihong Yang, Jianguo Wu, Li Zhang, Sangmin Lee, Dong-Ju Shin, Melanie Tran, Li Wang
H19 is an imprinted long non-coding RNA abundantly expressed in embryonic liver and repressed after birth. Here we show that H19 serves as a lipid sensor by synergizing with RNA-binding protein PTBP1 to modulate hepatic metabolic homeostasis. H19RNA interacts with PTBP1 to facilitate its association with SREBP1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are upregulated by fatty acids in hepatocytes and in diet-induced fatty liver, which further augments lipid accumulation...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29045475/association-between-rna-binding-protein-ptbp2-and-germ-cell-injury-in-an-experimentally-induced-unilateral-cryptorchidism-murine-model
#7
Xianming Dou, Jingjing Gao, Pan Gao, Dongdong Tang, Dangwei Peng, Jun Mao, Zhenyu Huang, Peng Chen, He Chen, Shengwei Ke, Chaozhao Liang, Xiansheng Zhang
RNA binding protein polypyrimidine tract binding protein 2 (Ptbp2) as a key alternative splicing regulator for male germ cell development is well established. However, its expression levels and role in cryptorchidism testes tissues has not been explored. Additionally, the molecular mechanism of heat stress impacts the correct proliferation and differentiation of germ cells is unclear. To investigate whether changes in Ptbp2 expression are correlated with heat stress-induced germ cell injury in testicular tissue, we used a murine model of intraperitoneal cryptorchidism with surgical operation...
2017: PloS One
https://www.readbyqxmd.com/read/29034946/spin-labelling-for-integrative-structure-modelling-a-case-study-of-the-polypyrimidine-tract-binding-protein-1-domains-in-complexes-with-short-rnas
#8
Christoph Gmeiner, Georg Dorn, Frédéric H T Allain, Gunnar Jeschke, Maxim Yulikov
A combined method, employing NMR and EPR spectroscopies, has demonstrated its strength in solving structures of protein/RNA and other types of biomolecular complexes. This method works particularly well when the large biomolecular complex consists of a limited number of rigid building blocks, such as RNA-binding protein domains (RBDs). A variety of spin labels is available for such studies, allowing for conventional as well as spectroscopically orthogonal double electron-electron resonance (DEER) measurements in EPR...
October 25, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28993438/architecture-and-distribution-of-introns-in-core-genes-of-four-fusarium-species
#9
Mmatshepho M Phasha, Brenda D Wingfield, Martin P A Coetzee, Quentin C Santana, Gerda Fourie, Emma T Steenkamp
Removal of introns from transcribed RNA represents a crucial step during the production of mRNA in eukaryotes. Available whole-genome sequences and expressed sequence tags (ESTs) have increased our knowledge of this process and revealed various commonalities among eukaryotes. However, certain aspects of intron structure and diversity are taxon-specific, which can complicate the accuracy of in silico gene prediction methods. Using core genes, we evaluated the distribution and architecture of Fusarium circinatum spliceosomal introns, and linked these characteristics to the accuracy of the predicted gene models of the genome of this fungus...
November 6, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28981396/cancer-specific-energy-metabolism-in-rhabdomyosarcoma-cells-is-regulated-by-microrna
#10
Nobuhiko Sugito, Kohei Taniguchi, Yuki Kuranaga, Maki Ohishi, Tomoyoshi Soga, Yuko Ito, Mitsuru Miyachi, Ken Kikuchi, Hajime Hosoi, Yukihiro Akao
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma and is most frequently found in children. In RMS, there are two major subtypes, that is, embryonal RMS and alveolar RMS (ARMS). ARMS has exclusively the worse prognosis and is caused by formation of the chimeric PAX3-FOXO1 gene. Regarding cancer, the Warburg effect is known as a feature of cancer-specific metabolism. Polypyrimidine tract-binding protein 1 (PTBP1), a splicer of pyruvate kinase muscle (PKM) mRNA, is a positive regulator of cancer-specific energy metabolism...
October 5, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28973454/interplay-between-ptb-and-mir-1285-at-the-p53-3-utr-modulates-the-levels-of-p53-and-its-isoform-%C3%AE-40p53%C3%AE
#11
Aanchal Katoch, Biju George, Amrutha Iyyappan, Debjit Khan, Saumitra Das
p53 and its translational isoform Δ40p53 are involved in many important cellular functions like cell cycle, cell proliferation, differentiation and metabolism. Expression of both the isoforms can be regulated at different steps. In this study, we explored the role of 3'UTR in regulating the expression of these two translational isoforms. We report that the trans acting factor, Polypyrimidine Tract Binding protein (PTB), also interacts specifically with 3'UTR of p53 mRNA and positively regulates expression of p53 isoforms...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28972001/the-metabolic-and-proliferative-state-of-vascular-adventitial-fibroblasts-in-pulmonary-hypertension-is-regulated-through-a-mir-124-ptbp1-pkm-axis
#12
Hui Zhang, Daren Wang, Min Li, Lydie Plecitá-Hlavatá, Angelo D'Alessandro, Jan Tauber, Suzette Riddle, Sushil Kumar, Amanda R Flockton, B Alexandre McKeon, Maria G Frid, Julie A Reisz, Paola Caruso, Karim C El Kasmi, Petr Ježek, Nicholas W Morrell, Cheng-Jun Hu, Kurt R Stenmark
Background -An emerging "metabolic theory" of pulmonary hypertension (PH) suggests that cellular and mitochondrial metabolic dysfunction underlies the pathology of this disease. We and others have previously demonstrated the existence of hyper-proliferative, apoptosis-resistant, pro-inflammatory adventitial fibroblasts from human and bovine hypertensive pulmonary arterial walls (PH-Fibs) exhibit constitutive reprogramming of glycolytic and mitochondrial metabolism, accompanied by an increased ratio of glucose catabolism through glycolysis versus the TCA cycle...
September 26, 2017: Circulation
https://www.readbyqxmd.com/read/28971999/identification-of-mir-124-as-a-major-regulator-of-enhanced-endothelial-cell-glycolysis-in-pulmonary-arterial-hypertension-via-ptbp1-and-pkm2
#13
Paola Caruso, Benjamin J Dunmore, Kenny Schlosser, Sandra Schoors, Claudia C Dos Santos, Carol Perez-Iratxeta, Jessie R Lavoie, Hui Zhang, Lu Long, Amanda R Flockton, Maria G Frid, Paul D Upton, Angelo D'Alessandro, Charaka Hadinnapola, Fedir N Kiskin, Mohamad Taha, Liam A Hurst, Mark L Ormiston, Akiko Hata, Kurt R Stenmark, Peter Carmeliet, Duncan J Stewart, Nicholas W Morrell
Background -Pulmonary arterial hypertension (PAH) is characterized by abnormal growth and enhanced glycolysis of pulmonary artery endothelial cells (PAECs). However, the mechanisms underlying alterations in energy production have not been identified. Methods -Here, we examined the miRNA and proteomic profiles of blood outgrowth endothelial cells (BOECs) from patients with heritable PAH (HPAH) due to mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene and patients with idiopathic PAH (IPAH) to determine mechanisms underlying abnormal endothelial glycolysis...
September 26, 2017: Circulation
https://www.readbyqxmd.com/read/28944929/oncogenic-mir%C3%A2-132-sustains-proliferation-and-self%C3%A2-renewal-potential-by-inhibition-of-polypyrimidine-tract%C3%A2-binding-protein-2-in-glioblastoma-cells
#14
Silong Lou, Jia Ji, Xin Cheng, Jian Ruan, Rong Li, Zhengjun Guo
Glioblastoma multiforme (GBM) is the leading type of brain tumor, exhibiting unlimited proliferation and invasion potential. The present study indicated that a high expression level of miR‑132 was detected in the neural subtype of GBM and predicted an unfavorable prognosis for patients from The Cancer Genome Atlas cohort (n=526). Cox hazard regression analysis demonstrated miR‑132 as an independent prognostic indicator for GBM patients. Further in vitro experiments indicated that miR‑132 promoted the proliferation and sphere formation of U87 cells...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28810637/binding-of-line-1-rna-to-psf-transcriptionally-promotes-gage6-and-regulates-cell-proliferation-and-tumor-formation-in-vitro
#15
Jiao Lv, Ziyi Zhao
Hepatocellular carcinoma (HCC) has one of the highest mortality rates among numerous types of cancer. It has been demonstrated that in hepatitis B (HBV)-associated HCC, the expression of chimeric fusion transcript HBx-long interspersed nuclear element-1 (LINE-1) initiated by HBV integration is correlated with hepatocarcinogenesis and poor patient survival rates. Furthermore, increased rates of LINE-1 hypomethylation have been detected in HCC tissues compared with adjacent tissues. This suggests that individual LINE-1 RNA (L1 RNA) serves an important role in the processes of hepatocarcinogenesis...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28763862/-a-screening-system-for-anti-metastatic-small-molecule-compounds-based-on-perinucleolar-compartment-prevalence-in-liver-cancer-cells
#16
F F Liu, G H Lou, Y N Liu, H H Zhu, Z Chen
Objective: To establish a screening system for anti-metastatic small-molecule compounds based on perinucleolar compartment (PNC) prevalence in liver cancer cells and to investigate its validity. Methods: Polypyrimidine tract-binding protein (PTB) monoclonal antibody was used to measure the PNC prevalence in HepG2, HepG2M, and Huh7 cells, and wound healing assay and transwell assay were used to analyze the migration and invasion abilities of hepatoma cells. HepG2M cells were used as the model for the screening of anti-metastatic small-molecule compounds, and after the treatment with the compounds A1, A4, and E696, qPCR was used to measure the expression of metastasis-related miRNAs (miR-141 and miR-200c)...
June 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28755480/g3bp1-interacts-directly-with-the-fmdv-ires-and-negatively-regulates-translation
#17
Alfonso Galan, Gloria Lozano, David Piñeiro, Encarnacion Martinez-Salas
RNA-protein interactions play a pivotal role in the function of picornavirus internal ribosome entry site (IRES) elements. Here we analysed the impact of Ras GTPase SH3 domain binding protein 1 (G3BP1) in the IRES activity of foot-and-mouth disease virus (FMDV). We found that G3BP1 interacts directly with three distinct sequences of the IRES element using RNA electrophoretic mobility-shift assays. Analysis of the interaction with domain 5 indicated that the G3BP1 binding-site is placed at the single-stranded region although it allows large sequence heterogeneity and the hairpin located upstream of this region enhances retarded complex formation...
October 2017: FEBS Journal
https://www.readbyqxmd.com/read/28726775/oroxylin-a-activates-pkm1-hnf4-alpha-to-induce-hepatoma-differentiation-and-block-cancer-progression
#18
Libin Wei, Yuanyuan Dai, Yuxin Zhou, Zihao He, Jingyue Yao, Li Zhao, Qinglong Guo, Lin Yang
Liver cancer is the second cause of death from cancer worldwide, without effective treatment. Traditional chemotherapy for liver cancer has big side effects for patients, whereas targeted drugs, such as sorafenib, commonly have drug resistance. Oroxylin A (OA) is the main bioactive flavonoids of Scutellariae radix, which has strong anti-hepatoma effect but low toxicity to normal tissue. To date, no differentiation-inducing agents have been reported to exert a curative effect on solid tumors. Here our results demonstrated that OA restrained the proliferation and induced differentiation of hepatoma both in vitro and in vivo, via inducing a high PKM1 (pyruvate kinase M1)/PKM2 (pyruvate kinase M2) ratio...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28722220/developing-new-targeting-strategy-for-androgen-receptor-variants-in-castration-resistant-prostate-cancer
#19
Bin Wang, U-Ging Lo, Kaijie Wu, Payal Kapur, Xiangyang Liu, Jun Huang, Wei Chen, Elizabeth Hernandez, John Santoyo, Shi-Hong Ma, Rey-Chen Pong, Dalin He, Yi-Qiang Cheng, Jer-Tsong Hsieh
The presence of androgen receptor variant 7 (AR-V7) variants becomes a significant hallmark of castration-resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand-binding domain. Currently, it still lacks an effective agent to target AR-V7 or AR-Vs in general. Here, we showed that a novel class of agents (thailanstatins, TSTs and spliceostatin A analogs) can significantly suppress the expression of AR-V7 mRNA and protein but in a less extent on the full-length AR expression...
November 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28695676/matrin3-binds-directly-to-intronic-pyrimidine-rich-sequences-and-controls-alternative-splicing
#20
Yuri Uemura, Takuya Oshima, Munetaka Yamamoto, Charles Jourdan Reyes, Pedro Henrique Costa Cruz, Toshiharu Shibuya, Yukio Kawahara
Matrin3 is an RNA-binding protein that is localized in the nuclear matrix. Although various roles in RNA metabolism have been reported for Matrin3, in vivo target RNAs to which Matrin3 binds directly have not been investigated comprehensively so far. Here, we show that Matrin3 binds predominantly to intronic regions of pre-mRNAs. Photoactivatable Ribonucleoside-Enhanced Cross-linking and Immunoprecipitation (PAR-CLIP) analysis using human neuronal cells showed that Matrin3 recognized pyrimidine-rich sequences as binding motifs, including the polypyrimidine tract, a splicing regulatory element...
September 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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