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polypyrimidine tract

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
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
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
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
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
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
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
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
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
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
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
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
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
Karen Yap, Yixin Xiao, Brad A Friedman, H Shawn Je, Eugene V Makeyev
Alternative splicing (AS) is an important source of proteome diversity in eukaryotes. However, how this affects protein repertoires at a single-cell level remains an open question. Here, we show that many 3'-terminal exons are persistently co-expressed with their alternatives in mammalian neurons. In an important example of this scenario, cell polarity gene Cdc42, a combination of polypyrimidine tract-binding, protein-dependent, and constitutive splicing mechanisms ensures a halfway switch from the general (E7) to the neuron-specific (E6) alternative 3'-terminal exon during neuronal differentiation...
May 10, 2016: Cell Reports
Yuanchao Xue, Hao Qian, Jing Hu, Bing Zhou, Yu Zhou, Xihao Hu, Aziz Karakhanyan, Zhiping Pang, Xiang-Dong Fu
Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, neuronal conversion is relatively inefficient in human cells compared to mouse cells. It has been unclear what might be the key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts (MEFs) into functional neurons. In human adult fibroblasts (HAFs), however, we unexpectedly found that invoking the documented PTB-REST-miR-124 loop generates only immature neurons...
June 2016: Nature Neuroscience
Javier Fernandez-Chamorro, Gloria Lozano, Juan Antonio Garcia-Martin, Jorge Ramajo, Ivan Dotu, Peter Clote, Encarnacion Martinez-Salas
The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems...
2016: Scientific Reports
Yucheng Zhao, Jun Luo, Sheng Xu, Wei Wang, Tingting Liu, Chao Han, Yijun Chen, Lingyi Kong
Peucedanum praeruptorum Dunn is one of the main traditional Chinese medicines producing coumarins and plenty of literatures are focused on the biosynthesis of coumarins. Quantitative real-time reverse transcription PCR (qRT-PCR) is a widely used method in studying the biosynthesis pathway and the selection of reference genes plays a crucial role in accurate normalization. To facilitate biosynthesis study of coumarins, twelve candidate reference genes were selected from the transcriptome database of P. praeruptorum according to previous studies...
2016: PloS One
Rita G Domingues, Inês Lago-Baldaia, Isabel Pereira-Castro, Joseph M Fachini, Liliana Oliveira, Danica Drpic, Nair Lopes, Telmo Henriques, Joel R Neilson, Alexandre M Carmo, Alexandra Moreira
T lymphocytes stimulated through their antigen receptor (TCR) preferentially express mRNA isoforms with shorter 3´ untranslated regions (3´-UTRs) derived from alternative pre-mRNA cleavage and polyadenylation (APA). However, the physiological relevance of APA programs remains poorly understood. CD5 is a T-cell surface glycoprotein that negatively regulates TCR signaling from the onset of T-cell activation. CD5 plays a pivotal role in mediating outcomes of cell survival or apoptosis, and may prevent both autoimmunity and cancer...
June 2016: European Journal of Immunology
Kohei Taniguchi, Miku Sakai, Nobuhiko Sugito, Minami Kumazaki, Haruka Shinohara, Nami Yamada, Tatsushi Nakayama, Hiroshi Ueda, Yoshihito Nakagawa, Yuko Ito, Manabu Futamura, Bunji Uno, Yoshinori Otsuki, Kazuhiro Yoshida, Kazuhisa Uchiyama, Yukihiro Akao
It is known that pyruvate kinase in muscle (PKM), which is a rate-limiting glycolytic enzyme, has essential roles in the Warburg effect and that expression of cancer-dominant PKM2 is increased by polypyrimidine tract-binding protein 1 (PTBP1), which is a splicer of the PKM gene. In other words, PKM2 acts as a promoter of the Warburg effect. Previously, we demonstrated that the Warburg effect was partially established by down-regulation of several microRNAs (miRs) that bind to PTBP1 and that ectopic expression of these miRs suppressed the Warburg effect...
April 5, 2016: Oncotarget
Carlos J Cáceres, Nataly Contreras, Jenniffer Angulo, Jorge Vera-Otarola, Constanza Pino-Ajenjo, Miriam Llorian, Melissa Ameur, Francisco Lisboa, Karla Pino, Fernando Lowy, Bruno Sargueil, Marcelo López-Lastra
The 5' untranslated region (UTR) of the full-length mRNA of the mouse mammary tumor virus (MMTV) harbors an internal ribosomal entry site (IRES). In this study, we show that the polypyrimidine tract-binding protein (PTB), an RNA-binding protein with four RNA recognition motifs (RRMs), binds to the MMTV 5' UTR stimulating its IRES activity. There are three isoforms of PTB: PTB1, PTB2, and PTB4. Results show that PTB1 and PTB4, but not PTB2, stimulate MMTV-IRES activity. PTB1 promotes MMTV-IRES-mediated initiation more strongly than PTB4...
May 2016: FEBS Journal
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