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polypyrimidine tract

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https://www.readbyqxmd.com/read/27926877/ptbp1-and-ptbp2-serve-both-specific-and-redundant-functions-in-neuronal-pre-mrna-splicing
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/lncrna-meg3-induces-cholestatic-liver-injury-by-interaction-with-ptbp1-to-facilitate-shp-mrna-decay
#7
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. 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 MEG3RNA followed by mass spectrometry, we identified RNA binding protein polypyrimidine tract-binding protein 1 (PTBP1) as a MEG3 interaction protein and validated their interaction by RNA immunoprecipitation (RIP)...
October 22, 2016: 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
#8
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-pkm-splicer-ptbp1
#9
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, which 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 down-regulated in gastric cancer clinical samples and human cell lines, whereas the protein expression level of PTBP1 was up-regulated in 80% of the 20 clinical samples of gastric cancer examined...
October 3, 2016: Cancer Science
https://www.readbyqxmd.com/read/27681424/ptbp1-and-ptbp2-repress-nonconserved-cryptic-exons
#10
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
https://www.readbyqxmd.com/read/27566151/alternative-splicing-of-u2af1-reveals-a-shared-repression-mechanism-for-duplicated-exons
#11
Jana Kralovicova, Igor Vorechovsky
The auxiliary factor of U2 small nuclear ribonucleoprotein (U2AF) facilitates branch point (BP) recognition and formation of lariat introns. The gene for the 35-kD subunit of U2AF gives rise to two protein isoforms (termed U2AF35a and U2AF35b) that are encoded by alternatively spliced exons 3 and Ab, respectively. The splicing recognition sequences of exon 3 are less favorable than exon Ab, yet U2AF35a expression is higher than U2AF35b across tissues. We show that U2AF35b repression is facilitated by weak, closely spaced BPs next to a long polypyrimidine tract of exon Ab...
August 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27547574/intron-gain-by-tandem-genomic-duplication-a-novel-case-in-a-potato-gene-encoding-rna-dependent-rna-polymerase
#12
Ming-Yue Ma, Xin-Ran Lan, Deng-Ke Niu
The origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. However, the mechanisms underlying intron gain remain unclear because there are few proven cases of recently gained introns. In an RNA-dependent RNA polymerase (RdRp) gene, we found that a tandem duplication occurred after the divergence of potato and its wild relatives among other Solanum plants. The duplicated sequence crosses the intron-exon boundary of the first intron and the second exon...
2016: PeerJ
https://www.readbyqxmd.com/read/27528752/functional-interactions-between-polypyrimidine-tract-binding-protein-and-pri-peptide-ligand-containing-proteins
#13
REVIEW
Miguel B Coelho, David B Ascher, Clare Gooding, Emma Lang, Hannah Maude, David Turner, Miriam Llorian, Douglas E V Pires, Jan Attig, Christopher W J Smith
Polypyrimidine tract binding protein (PTBP1) is a heterogeneous nuclear ribonucleoprotein (hnRNP) that plays roles in most stages of the life-cycle of pre-mRNA and mRNAs in the nucleus and cytoplasm. PTBP1 has four RNA binding domains of the RNA recognition motif (RRM) family, each of which can bind to pyrimidine motifs. In addition, RRM2 can interact via its dorsal surface with proteins containing short peptide ligands known as PTB RRM2 interacting (PRI) motifs, originally found in the protein Raver1. Here we review our recent progress in understanding the interactions of PTB with RNA and with various proteins containing PRI ligands...
August 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27513449/the-rna-binding-protein-polypyrimidine-tract-binding-protein-1-ptbp1-is-a-key-regulator-of-cd4-t-cell-activation
#14
James La Porta, Rodrigo Matus-Nicodemos, Aníbal Valentín-Acevedo, Lori R Covey
We have previously shown that the RNA binding protein, polypyrimidine tract-binding protein (PTBP1) plays a critical role in regulating the expression of CD40L in activated CD4 T cells. This is achieved mechanistically through message stabilization at late times of activation as well as by altered distribution of CD40L mRNA within distinct cellular compartments. PTBP1 has been implicated in many different processes, however whether PTBP1 plays a broader role in CD4 T cell activation is not known. To examine this question, experiments were designed to introduce shRNA into primary human CD4 T cells to achieve decreased, but not complete ablation of PTBP1 expression...
2016: PloS One
https://www.readbyqxmd.com/read/27367564/ptbp1-modulation-of-mcl1-expression-regulates-cellular-apoptosis-induced-by-antitubulin-chemotherapeutics
#15
J Cui, W J Placzek
Myeloid cell leukemia sequence 1 (MCL1), an anti-apoptotic BCL2 family protein, is a key regulator of intrinsic apoptosis. Normal cells require strict control over MCL1 expression with aberrant MCL1 expression linked to the emergence of various diseases and chemoresistance. Previous studies have detailed how MCL1 expression is regulated by multiple mechanisms both transcriptionally and translationally. However, characterization of the post-transcriptional regulators of MCL1 mRNA is limited. Polypyrimidine tract binding protein 1 (PTBP1) is a known regulator of post-transcriptional gene expression that can control mRNA splicing, translation, stability and localization...
October 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27358902/identification-of-neural-stem-cell-differentiation-repressor-complex-pnky-ptbp1
#16
Ioannis Grammatikakis, Myriam Gorospe
Splicing increases immensely the complexity of gene products expressed in the cell. The precise regulation of splicing is critical for the development, homeostasis, and function of all tissues in the body, including those comprising the neural system. Ramos et al. recently identified Pnky as a long noncoding RNA expressed selectively in neural tissues that was implicated in the transition of neural stem cells (NSCs) to mature neurons. Pnky actions appeared to be mediated by its interaction with the splicing factor and RNA-binding protein (RBP) polypyrimidine tract-binding protein (PTBP1), as silencing either Pnky or PTBP1 modulated in similar ways the patterns of spliced and expressed mRNAs in the cell...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27317697/the-alternative-splicing-program-of-differentiated-smooth-muscle-cells-involves-concerted-non-productive-splicing-of-post-transcriptional-regulators
#17
Miriam Llorian, Clare Gooding, Nicolas Bellora, Martina Hallegger, Adrian Buckroyd, Xiao Wang, Dipen Rajgor, Melis Kayikci, Jack Feltham, Jernej Ule, Eduardo Eyras, Christopher W J Smith
Alternative splicing (AS) is a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1)...
June 17, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27252533/two-polypyrimidine-tracts-in-intron-4-of-the-major-immediate-early-gene-are-critical-for-gene-expression-switching-from-ie1-to-ie2-and-for-replication-of-human-cytomegalovirus
#18
Wangheng Hou, Lilith Torres, Ruth Cruz-Cosme, Fernando Arroyo, Luis Irizarry, Dalia Luciano, Arturo Márquez, Leslie L Rivera, Antonio L Sala, Min-Hua Luo, Qiyi Tang
UNLABELLED: The human cytomegalovirus (HCMV) major immediate early (MIE) gene is essential for viral replication. The most abundant products encoded by the MIE gene include IE1 and IE2. Genes of IE1 and IE2 share the MIE promoter (MIEP), the first 3 exons, and the first 2 introns. IE1 is expressed earlier than IE2 after CMV infection or MIE gene transfection. In this study, we identified 2 polypyrimidine (Py) tracts in intron 4 (between exons 4 and 5) that are responsible for transcriptional switching from IE1 to IE2...
August 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27200013/selection-and-validation-of-appropriate-reference-genes-for-quantitative-real-time-pcr-analysis-of-gene-expression-in-lycoris-aurea
#19
Rui Ma, Sheng Xu, Yucheng Zhao, Bing Xia, Ren Wang
Lycoris aurea (L' Hér.) Herb, a perennial grass species, produces a unique variety of pharmacologically active Amaryllidaceae alkaloids. However, the key enzymes and their expression pattern involved in the biosynthesis of Amaryllidaceae alkaloids (especially for galanthamine) are far from being fully understood. Quantitative real-time polymerase chain reaction (qRT-PCR), a commonly used method for quantifying gene expression, requires stable reference genes to normalize its data. In this study, to choose the appropriate reference genes under different experimental conditions, 14 genes including YLS8 (mitosis protein YLS8), CYP2 (Cyclophilin 2), CYP 1 (Cyclophilin 1), TIP41 (TIP41-like protein), EXP2 (Expressed protein 2), PTBP1 (Polypyrimidine tract-binding protein 1), EXP1 (Expressed protein 1), PP2A (Serine/threonine-protein phosphatase 2A), β-TUB (β-tubulin), α-TUB (α-tubulin), EF1-α (Elongation factor 1-α), UBC (Ubiquitin-conjugating enzyme), ACT (Actin) and GAPDH (Glyceraldehyde 3-phosphate dehydrogenase) were selected from the transcriptome datasets of L...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27172199/n-ethyl-n-nitrosourea-enu-mutagenesis-reveals-an-intronic-residue-critical-for-caenorhabditis-elegans-3-splice-site-function-in-vivo
#20
Omar A Itani, Stephane Flibotte, Kathleen J Dumas, Chunfang Guo, Thomas Blumenthal, Patrick J Hu
Metazoan introns contain a polypyrimidine tract immediately upstream of the AG dinucleotide that defines the 3' splice site. In the nematode Caenorhabditis elegans, 3' splice sites are characterized by a highly conserved UUUUCAG/R octamer motif. While the conservation of pyrimidines in this motif is strongly suggestive of their importance in pre-mRNA splicing, in vivo evidence in support of this is lacking. In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen in Caenorhabditis elegans, we have isolated a strain containing a point mutation in the octamer motif of a 3' splice site in the daf-12 gene...
2016: G3: Genes—Genomes—Genetics
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