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polypyrimidine tract

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https://www.readbyqxmd.com/read/28414323/pyrimidine-tract-binding-protein-1-mediates-pyruvate-kinase-m2-dependent-phosphorylation-of-signal-transducer-and-activator-of-transcription-3-and-oncogenesis-in-anaplastic-large-cell-lymphoma
#1
Steven R Hwang, Carlos Murga-Zamalloa, Noah Brown, Johnvesly Basappa, Scott Rp McDonnell, Veronica Mendoza-Reinoso, Venkatesha Basrur, Ryan Wilcox, Kojo Elenitoba-Johnson, Megan S Lim
PKM2 (pyruvate kinase M2), a critical regulator of glycolysis, is phosphorylated by numerous growth factor receptors and oncogenic tyrosine kinases including NPM-ALK which is expressed in a subset of aggressive T-cell non-Hodgkin lymphomas known as anaplastic large cell lymphoma, ALK-positive. Our previous work demonstrated that phosphorylation of Y105-PKM2 by NPM-ALK regulates a major metabolic shift to promote lymphomagenesis. In addition to its role in metabolism, recent studies have shown that PKM2 promotes oncogenesis by phosphorylating nuclear STAT3 (signal transducer and activator of transcription 3) and regulating transcription of genes involved in cell survival and proliferation...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28404950/high-expression-of-ptbp1-promote-invasion-of-colorectal-cancer-by-alternative-splicing-of-cortactin
#2
Zhi-Na Wang, Dan Liu, Bin Yin, Wen-Yi Ju, Hui-Zhong Qiu, Yi Xiao, Yuan-Jia Chen, Xiao-Zhong Peng, Chong-Mei Lu
Polypyrimidine tract-binding protein 1 (PTBP1) involving in almost all steps of mRNA regulation including alternative splicing metabolism during tumorigenesis due to its RNA-binding activity. Initially, we found that high expressed PTBP1 and poor prognosis was interrelated in colorectal cancer (CRC) patients with stages II and III CRC, which widely different in prognosis and treatment, by immunohistochemistry. PTBP1 was also upregulated in colon cancer cell lines. In our study, knockdown of PTBP1 by siRNA transfection decreased cell proliferation and invasion in vitro...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28393214/a-novel-mutation-c-121%C3%A2-13t-a-in-the-polypyrimidine-tract-of-the-splice-acceptor-site-of-intron-2-causes-exon-3-skipping-in-mitochondrial-acetoacetyl-coa-thiolase-gene
#3
Yuka Aoyama, Hideo Sasai, Elsayed Abdelkreem, Hiroki Otsuka, Mina Nakama, Sandeep Kumar, Shrikiran Aroor, Anju Shukla, Toshiyuki Fukao
Mitochondrial acetoacetyl-CoA thiolase (T2) (gene symbol: ACAT1) deficiency is an autosomal recessive disorder affecting isoleucine catabolism and ketone body utilization. In this study, mutational analysis of an Indian T2-deficient patient revealed a homozygous mutation (c.121‑13T>A) located at the polypyrimidine tract of the splice acceptor site of intron 2, and exon 3 skipping was identified by cDNA analysis using cycloheximide. We made three mutant constructs (c.121‑13T>A, T>C, and T>G substitutions) followed by making a wild-type minigene construct that included an ACAT1 segment from exon 2 to 4 for a splicing experiment...
April 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28346450/structural-modeling-of-protein-rna-complexes-using-crosslinking-of-segmentally-isotope-labeled-rna-and-ms-ms
#4
Georg Dorn, Alexander Leitner, Julien Boudet, Sébastien Campagne, Christine von Schroetter, Ahmed Moursy, Ruedi Aebersold, Frédéric H-T Allain
Ribonucleoproteins (RNPs) are key regulators of cellular function. We established an efficient approach, crosslinking of segmentally isotope-labeled RNA and tandem mass spectrometry (CLIR-MS/MS), to localize protein-RNA interactions simultaneously at amino acid and nucleotide resolution. The approach was tested on polypyrimidine tract binding protein 1 and U1 small nuclear RNP. Our method provides distance restraints to support integrative atomic-scale structural modeling and to gain mechanistic insights into RNP-regulated processes...
March 27, 2017: Nature Methods
https://www.readbyqxmd.com/read/28339459/functional-classification-of-dna-variants-by-hybrid-minigenes-identification-of-30-spliceogenic-variants-of-brca2-exons-17-and-18
#5
Eugenia Fraile-Bethencourt, Beatriz Díez-Gómez, Valeria Velásquez-Zapata, Alberto Acedo, David J Sanz, Eladio A Velasco
Mutation screening of the breast cancer genes BRCA1 and BRCA2 identifies a large fraction of variants of uncertain clinical significance (VUS) whose functional and clinical interpretations pose a challenge for genomic medicine. Likewise, an increasing amount of evidence indicates that genetic variants can have deleterious effects on pre-mRNA splicing. Our goal was to investigate the impact on splicing of a set of reported variants of BRCA2 exons 17 and 18 to assess their role in hereditary breast cancer and to identify critical regulatory elements that may constitute hotspots for spliceogenic variants...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28337374/polypyrimidine-tract-binding-protein-1-promotes-proliferation-migration-and-invasion-in-clear-cell-renal-cell-carcinoma-by-regulating-alternative-splicing-of-pkm
#6
Junyi Jiang, Xu Chen, Hao Liu, Jing Shao, Ruihui Xie, Peng Gu, Chaohui Duan
Polypyrimidine Tract-Binding Protein 1 (PTBP1) is an essential RNA-binding protein that regulates diverse biological events through regulating alternative splice of mRNA. PTBP1 induces cancer-promoting splice variants and is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of PTBP1 in clear-cell renal cell carcinoma (ccRCC) are unclear. We investigated PTBP1 expression in 533 ccRCC patients from TCGA and 30 ccRCC patients by immunohistochemistry, and found that PTBP1 expression levels were significantly increased in ccRCC tissues and that high PTBP1 expression was closely correlated with advanced tumor stage, AJCC stage and poor prognosis...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28222070/inhibition-of-polypyrimidine-tract-binding-protein-3-induces-apoptosis-and-cell-cycle-arrest-and-enhances-the-cytotoxicity-of-5-fluorouracil-in-gastric-cancer-cells
#7
Xin Liang, Haiyang Shi, Liyan Yang, Cen Qiu, Shengchao Lin, Yingxue Qi, Jiyu Li, Aiguang Zhao, Jianwen Liu
BACKGROUND: Human polypyrimidine tract binding protein 3 (PTBP3) was first discovered in 1999 and has been well characterised as a differentiation regulator. However, its role in human cancer has rarely been reported. Our previous study revealed increased PTBP3 protein level in gastric cancer tissues. Downregulation of PTBP3 suppressed the proliferation and differentiation of gastric cancer cells in vivo. METHODS: PTBP3 mRNA levels in human gastric cancer and adjuvant non-tumour tissues were detected...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28208608/multiple-mobile-mrna-signals-regulate-tuber-development-in-potato
#8
REVIEW
David J Hannapel, Anjan K Banerjee
Included among the many signals that traffic through the sieve element system are full-length mRNAs that function to respond to the environment and to regulate development. In potato, several mRNAs that encode transcription factors from the three-amino-loop-extension (TALE) superfamily move from leaves to roots and stolons via the phloem to control growth and signal the onset of tuber formation. This RNA transport is enhanced by short-day conditions and is facilitated by RNA-binding proteins from the polypyrimidine tract-binding family of proteins...
February 10, 2017: Plants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28202388/viral-vector-reprogramming-of-adult-resident-striatal-oligodendrocytes-into-functional-neurons
#9
Marc S Weinberg, Hugh E Criswell, Sara K Powell, Aadra P Bhatt, Thomas J McCown
Recent advances suggest that in vivo reprogramming of endogenous cell populations provides a viable alternative for neuron replacement. Astrocytes and oligodendrocyte precursor cells can be induced to transdifferentiate into neurons in the CNS, but, in these instances, reprogramming requires either transgenic mice or retroviral-mediated gene expression. We developed a microRNA (miRNA)-GFP construct that in vitro significantly reduced the expression of polypyrimidine tract-binding protein, and, subsequently, we packaged this construct in a novel oligodendrocyte preferring adeno-associated virus vector...
April 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#10
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27926877/ptbp1-and-ptbp2-serve-both-specific-and-redundant-functions-in-neuronal-pre-mrna-splicing
#11
John K Vuong, Chia-Ho Lin, Min Zhang, Liang Chen, Douglas L Black, Sika Zheng
Families of alternative splicing regulators often contain multiple paralogs presumed to fulfill different functions. Polypyrimidine tract binding proteins PTBP1 and PTBP2 reprogram developmental pre-mRNA splicing in neurons, but how their regulatory networks differ is not understood. To compare their targeting, we generated a knockin allele that conditionally expresses PTBP1. Bred to a Ptbp2 knockout, the transgene allowed us to compare the developmental and molecular phenotypes of mice expressing only PTBP1, only PTBP2, or neither protein in the brain...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27897224/tgf-%C3%AE-1-induces-polypyrimidine-tract-binding-protein-to-alter-fibroblasts-proliferation-and-fibronectin-deposition-in-keloid
#12
Hu Jiao, Ping Dong, Li Yan, Zhigang Yang, Xiaoyan Lv, Qiuchen Li, Xianlei Zong, Jincai Fan, Xin Fu, Xia Liu, Ran Xiao
Human dermal fibrotic disease keloid has been a clinical challenge because of its tumour-like growth and the lack of effective therapy. Dysregulated alternative splicing events have been demonstrated in tumours and fibrosis. In the current study, for the first time, it was demonstrated that the splicing regulator polypyrimidine tract-binding protein (PTB), which plays a pivotal role in tumour proliferation, invasion and metastasis, is overexpressed in keloid tissues and fibroblasts. Additionally, TGF-β1 upregulated the expressions of PTB and its upstream regulator, C-MYC, in keloid fibroblasts...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882870/large-scale-remodeling-of-a-repressed-exon-ribonucleoprotein-to-an-exon-definition-complex-active-for-splicing
#13
Somsakul Pop Wongpalee, Ajay Vashisht, Shalini Sharma, Darryl Chui, James A Wohlschlegel, Douglas L Black
Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition...
November 24, 2016: ELife
https://www.readbyqxmd.com/read/27836735/polypyrimidine-tract-binding-protein-1-mediated-down-regulation-of-atg10-facilitates-metastasis-of-colorectal-cancer-cells
#14
Yoon Kyung Jo, Seon Ae Roh, Heejin Lee, Na Yeon Park, Eun Sun Choi, Ju-Hee Oh, So Jung Park, Ji Hyun Shin, Young-Ah Suh, Eun Kyung Lee, Dong-Hyung Cho, Jin Cheon Kim
Autophagy plays complex roles in tumor initiation and development, and the expression of autophagy-related genes (ATGs) is differentially regulated in various cancer cells, depending on their environment. In this study, we analyzed the expressional relationship between polypyrimidine tract-binding protein 1 (PTBP1) and ATG10 in metastatic colorectal cancer. PTBP1 is associated with tumor metastasis in primary colorectal tumors and colorectal cancer liver metastasis (CLM) tissues. In addition, PTPB1 directly interacts with mRNA of ATG10, and regulates ATG10 expression level in colorectal cancer cells...
January 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27799531/recognition-of-the-3-splice-site-rna-by-the-u2af-heterodimer-involves-a-dynamic-population-shift
#15
Lena Voith von Voithenberg, Carolina Sánchez-Rico, Hyun-Seo Kang, Tobias Madl, Katia Zanier, Anders Barth, Lisa R Warner, Michael Sattler, Don C Lamb
An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27791185/control-of-embryonic-stem-cell-self-renewal-and-differentiation-via-coordinated-alternative-splicing-and-translation-of-yy2
#16
Soroush Tahmasebi, Seyed Mehdi Jafarnejad, Ingrid S Tam, Thomas Gonatopoulos-Pournatzis, Edna Matta-Camacho, Yoshinori Tsukumo, Akiko Yanagiya, Wencheng Li, Yaser Atlasi, Maxime Caron, Ulrich Braunschweig, Dana Pearl, Arkady Khoutorsky, Christos G Gkogkas, Robert Nadon, Guillaume Bourque, Xiang-Jiao Yang, Bin Tian, Hendrik G Stunnenberg, Yojiro Yamanaka, Benjamin J Blencowe, Vincent Giguère, Nahum Sonenberg
Translational control of gene expression plays a key role during the early phases of embryonic development. Here we describe a transcriptional regulator of mouse embryonic stem cells (mESCs), Yin-yang 2 (YY2), that is controlled by the translation inhibitors, Eukaryotic initiation factor 4E-binding proteins (4E-BPs). YY2 plays a critical role in regulating mESC functions through control of key pluripotency factors, including Octamer-binding protein 4 (Oct4) and Estrogen-related receptor-β (Esrrb). Importantly, overexpression of YY2 directs the differentiation of mESCs into cardiovascular lineages...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27770549/long-noncoding-rna-meg3-induces-cholestatic-liver-injury-by-interaction-with-ptbp1-to-facilitate-shp-mrna-decay
#17
Li Zhang, Zhihong Yang, Jocelyn Trottier, Olivier Barbier, Li Wang
Bile acids (BAs) play critical physiological functions in cholesterol homeostasis, and deregulation of BA metabolism causes cholestatic liver injury. The long noncoding RNA maternally expressed gene 3 (MEG3) was recently shown as a potential tumor suppressor; however, its basic hepatic function remains elusive. Using RNA pull-down with biotin-labeled sense or anti-sense MEG 3RNA followed by mass spectrometry, we identified RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interacting protein and validated their interaction by RNA immunoprecipitation (RIP)...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27699280/ptb-and-tiar-binding-to-insulin-mrna-3-and-5-utrs-implications-for-insulin-biosynthesis-and-messenger-stability
#18
Rikard G Fred, Syrina Mehrabi, Christopher M Adams, Nils Welsh
OBJECTIVES: Insulin expression is highly controlled on the posttranscriptional level. The RNA binding proteins (RBPs) responsible for this result are still largely unknown. METHODS AND RESULTS: To identify RBPs that bind to insulin mRNA we performed mass spectrometry analysis on proteins that bound synthetic oligonucloetides mimicing the 5'- and the 3'-untranslated regions (UTRs) of rat and human insulin mRNA in vitro. We observed that the RBPs heterogeneous nuclear ribonucleoprotein (hnRNP) U, polypyrimidine tract binding protein (PTB), hnRNP L and T-cell restricted intracellular antigen 1-related protein (TIA-1-related protein; TIAR) bind to insulin mRNA sequences, and that the in vitro binding affinity of these RBPs changed when INS-1 cells were exposed to glucose, 3-isobutyl-1-methylxanthine (IBMX) or nitric oxide...
September 2016: Heliyon
https://www.readbyqxmd.com/read/27696637/mir-133b-inhibits-growth-of-human-gastric-cancer-cells-by-silencing-pyruvate-kinase-muscle-splicer-polypyrimidine-tract-binding-protein-1
#19
Taro Sugiyama, Kohei Taniguchi, Nobuhisa Matsuhashi, Toshihiro Tajirika, Manabu Futamura, Tomoaki Takai, Yukihiro Akao, Kazuhiro Yoshida
The metabolism in tumor cells shifts from oxidative phosphorylation to glycolysis even in an aerobic environment. This phenomenon is known as the Warburg effect. This effect is regulated mainly by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the mRNA for the rate-limiting enzymes of glycolysis, pyruvate kinase muscle 1 and 2 (PKM1 and PKM2). In the present study, we demonstrated that miR-133b reduced PTBP1 expression at translational level and that the expression levels of miR-133b were significantly downregulated in gastric cancer clinical samples and human cell lines, whereas the protein expression level of PTBP1 was upregulated in 80% of the 20 clinical samples of gastric cancer examined...
December 2016: Cancer Science
https://www.readbyqxmd.com/read/27681424/ptbp1-and-ptbp2-repress-nonconserved-cryptic-exons
#20
Jonathan P Ling, Resham Chhabra, Jonathan D Merran, Paul M Schaughency, Sarah J Wheelan, Jeffry L Corden, Philip C Wong
The fidelity of RNA splicing is maintained by a network of factors, but the molecular mechanisms that govern this process have yet to be fully elucidated. We previously found that TDP-43, an RNA-binding protein implicated in neurodegenerative disease, utilizes UG microsatellites to repress nonconserved cryptic exons and prevent their incorporation into mRNA. Here, we report that two well-characterized splicing factors, polypyrimidine tract-binding protein 1 (PTBP1) and polypyrimidine tract-binding protein 2 (PTBP2), are also nonconserved cryptic exon repressors...
September 27, 2016: Cell Reports
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