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HnRNP G

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https://www.readbyqxmd.com/read/28570076/insight-into-the-complexity-of-the-i-motif-and-g-quadruplex-dna-structures-formed-in-the-kras-promoter-and-subsequent-drug-induced-gene-repression
#1
Christine E Kaiser, Natalie A Van Ert, Prashansa Agrawal, Reena Chawla, Danzhou Yang, Laurence H Hurley
Activating KRAS mutations frequently occur in pancreatic, colorectal, and lung adenocarcinomas. While many attempts have been made to target oncogenic KRAS, no clinically useful therapies currently exist. Most efforts to target KRAS have focused on inhibiting the mutant protein; a less explored approach involves targeting KRAS at the transcriptional level. The promoter element of the KRAS gene contains a GC-rich nuclease hypersensitive site with three potential DNA secondary structure-forming regions. These are referred to as the Near-, Mid-, and Far-regions, on the basis of their proximity to the transcription start site...
June 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28510424/structure-dependent-binding-of-hnrnpa1-to-telomere-rna
#2
Xiao Liu, Takumi Ishizuka, Hong-Liang Bao, Kei Wada, Yuma Takeda, Keisuke Iida, Kazuo Nagasawa, Danzhou Yang, Yan Xu
Telomeric repeat-containing RNA is a new noncoding RNA molecule that performs various biofunctions. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an RNA-binding protein involved in the telomere maintenance machinery. To date, little is known about how hnRNPA1 binds to telomeric RNA. In this study, we investigated the binding affinity and recognition mechanism of telomere RNA with the RNA recognition motif of hnRNPA1. Using the photochemical cross-linking method, we showed that the telomere RNA G-quadruplex with loops is important in the interaction of telomere RNA with hnRNPA1...
June 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28428548/antiviral-activities-of-schizonepeta-tenuifolia-briq-against-enterovirus-71-in-vitro-and-in-vivo
#3
Sin-Guang Chen, Mei-Ling Cheng, Kuan-Hsing Chen, Jim-Tong Horng, Ching-Chuan Liu, Shih-Min Wang, Hiroaki Sakurai, Yann-Lii Leu, Shulhn-Der Wang, Hung-Yao Ho
No effective drug is currently available for treatment of enterovirus 71 (EV71) infection. Schizonepeta tenuifolia Briq. (ST) has been used as a herbal constituent of traditional Chinese medicine. We studied whether the aqueous extract of Schizonepeta tenuifolia Briq (STE) has antiviral activity. STE inhibited replication of EV71, as evident by its ability to diminish plaque formation and cytopathic effect induced by EV71, and to inhibit the synthesis of viral RNA and protein. Moreover, daily single-dose STE treatment significantly improved the survival of EV71-infected mice, and ameliorated the symptoms...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424160/heterogeneous-nuclear-ribonucleoprotein-f-stimulates-sirtuin-1-gene-expression-and-attenuates-nephropathy-progression-in-diabetic-mice
#4
Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Anindya Ghosh, Chin-Han Wu, Jean-Francois Cailhier, Jean Ethier, Jean-Baptiste Lattouf, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the mechanism of heterogeneous nuclear ribonucleoprotein F (hnRNP F) renoprotective action on a type 2 diabetic (T2D) (db/db) mice. Immortalized rat renal proximal tubular cells (IRPTCs) and human T2D kidneys were also studied. Db/db mice developed hyperglycemia, oxidative stress and nephropathy at age 20 weeks compared to their db/m littermates. These abnormalities, with the exception of hyperglycemia, were attenuated in db/db hnRNP F-transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs...
April 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28411275/odorant-sensory-input-modulates-dna-secondary-structure-formation-and-heterogeneous-ribonucleoprotein-recruitment-on-the-tyrosine-hydroxylase-and-glutamic-acid-decarboxylase-1-promoters-in-the-olfactory-bulb
#5
Meng Wang, Elizabeth Cai, Nana Fujiwara, Lilah Fones, Elizabeth Brown, Yuchio Yanagawa, John W Cave
Adaptation of neural circuits to changes in sensory input can modify several cellular processes within neurons, including neurotransmitter biosynthesis levels. For a subset of olfactory bulb interneurons, activity-dependent changes in GABA are reflected by corresponding changes in Glutamate decarboxylase 1 (Gad1) expression levels. Mechanisms regulating Gad1 promoter activity are poorly understood, but here we show that a conserved G:C-rich region in the mouse Gad1 proximal promoter region both recruits heterogeneous nuclear ribonucleoproteins (hnRNPs) that facilitate transcription and forms single-stranded DNA secondary structures associated with transcriptional repression...
May 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28380354/the-drosophila-hnrnp-f-h-homolog-glorund-uses-two-distinct-rna-binding-modes-to-diversify-target-recognition
#6
Joel V Tamayo, Takamasa Teramoto, Seema Chatterjee, Traci M Tanaka Hall, Elizabeth R Gavis
The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs...
April 4, 2017: Cell Reports
https://www.readbyqxmd.com/read/28338097/the-cellular-protein-hnrnp-a2-b1-enhances-hiv-1-transcription-by-unfolding-ltr-promoter-g-quadruplexes
#7
Matteo Scalabrin, Ilaria Frasson, Emanuela Ruggiero, Rosalba Perrone, Elena Tosoni, Sara Lago, Martina Tassinari, Giorgio Palù, Sara N Richter
G-quadruplexes are four-stranded conformations of nucleic acids that act as cellular epigenetic regulators. A dynamic G-quadruplex forming region in the HIV-1 LTR promoter represses HIV-1 transcription when in the folded conformation. This activity is enhanced by nucleolin, which induces and stabilizes the HIV-1 LTR G-quadruplexes. In this work by a combined pull-down/mass spectrometry approach, we consistently found hnRNP A2/B1 as an additional LTR-G-quadruplex interacting protein. Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324005/insulin-inhibits-nrf2-gene-expression-via-heterogeneous-nuclear-ribonucleoprotein-f-k-in-diabetic-mice
#8
Anindya Ghosh, Shaaban Abdo, Shuiling Zhao, Chin-Han Wu, Yixuan Shi, Chao-Sheng Lo, Isabelle Chenier, Thierry Alquier, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
Oxidative stress induces endogenous antioxidants via nuclear factor erythroid 2-related factor 2 (Nrf2), potentially preventing tissue injury. We investigated whether insulin affects renal Nrf2 expression in type 1 diabetes (T1D) and studied its underlying mechanism. Insulin normalized hyperglycemia, hypertension, oxidative stress, and renal injury; inhibited renal Nrf2 and angiotensinogen (Agt) gene expression; and upregulated heterogeneous nuclear ribonucleoprotein F and K (hnRNP F and hnRNP K) expression in Akita mice with T1D...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/27940037/the-g-quadruplex-specific-rna-helicase-dhx36-regulates-p53-pre-mrna-3-end-processing-following-uv-induced-dna-damage
#9
Michelle Newman, Rym Sfaxi, Abhijit Saha, David Monchaud, Marie-Paule Teulade-Fichou, Stéphan Vagner
Pre-mRNA 3'-end processing, the process through which almost all eukaryotic mRNAs acquire a poly(A) tail is generally inhibited during the cellular DNA damage response leading to a profound impact on the level of protein expression since unprocessed transcripts at the 3'-end will be degraded or unable to be transported to the cytoplasm. However, a compensatory mechanism involving the binding of the hnRNP H/F family of RNA binding proteins to an RNA G-quadruplex (G4) structure located in the vicinity of a polyadenylation site has previously been described to allow the transcript encoding the p53 tumour suppressor protein to be properly processed during DNA damage and to provide the cells with a way to react to DNA damage...
December 7, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27880931/an-xist-related-small-rna-regulates-kras-g-quadruplex-formation-beyond-x-inactivation
#10
Yuli C Chang, Chien-Chih Chiu, Chung-Yee Yuo, Wen-Ling Chan, Ya-Sian Chang, Wen-Hsin Chang, Shou-Mei Wu, Han-Lin Chou, Ta-Chih Liu, Chi-Yu Lu, Wen-Kuang Yang, Jan-Gowth Chang
X-inactive-specific transcript (XIST), a long non-coding RNA, is essential for the initiation of X-chromosome inactivation. However, little is known about other roles of XIST in the physiological process in eukaryotic cells. In this study, the bioinformatics approaches revealed XIST could be processed into a small non-coding RNA XPi2. The XPi2 RNA was confirmed by a northern blot assay; its expression was gender-independent, suggesting the role of XPi2 was beyond X-chromosome inactivation. The pull-down assay combined with LC-MS-MS identified two XPi2-associated proteins, nucleolin and hnRNP A1, connected to the formation of G-quadruplex...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27699280/ptb-and-tiar-binding-to-insulin-mrna-3-and-5-utrs-implications-for-insulin-biosynthesis-and-messenger-stability
#11
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/27669098/a-mechanosensor-mechanism-controls-the-g-quadruplex-i-motif-molecular-switch-in-the-myc-promoter-nhe-iii1
#12
Caleb Sutherland, Yunxi Cui, Hanbin Mao, Laurence H Hurley
MYC is overexpressed in many different cancer types and is an intensively studied oncogene because of its contributions to tumorigenesis. The regulation of MYC is complex, and the NHE III1 and FUSE elements rely upon noncanonical DNA structures and transcriptionally induced negative superhelicity. In the NHE III1 only the G-quadruplex has been extensively studied, whereas the role of the i-motif, formed on the opposite C-rich strand, is much less understood. We demonstrate here that the i-motif is formed within the 4CT element and is recognized by hnRNP K, which leads to a low level of transcription activation...
October 11, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27651450/competitive-regulation-of-alternative-splicing-and-alternative-polyadenylation-by-hnrnp-h-and-cstf64-determines-acetylcholinesterase-isoforms
#13
Mohammad Nazim, Akio Masuda, Mohammad Alinoor Rahman, Farhana Nasrin, Jun-Ichi Takeda, Kenji Ohe, Bisei Ohkawara, Mikako Ito, Kinji Ohno
Acetylcholinesterase (AChE), encoded by the ACHE gene, hydrolyzes the neurotransmitter acetylcholine to terminate synaptic transmission. Alternative splicing close to the 3' end generates three distinct isoforms of AChET, AChEH and AChER We found that hnRNP H binds to two specific G-runs in exon 5a of human ACHE and activates the distal alternative 3' splice site (ss) between exons 5a and 5b to generate AChET Specific effect of hnRNP H was corroborated by siRNA-mediated knockdown and artificial tethering of hnRNP H...
September 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27623008/the-c9orf72-ggggcc-expansion-forms-rna-g-quadruplex-inclusions-and-sequesters-hnrnp-h-to-disrupt-splicing-in-als-brains
#14
Erin G Conlon, Lei Lu, Aarti Sharma, Takashi Yamazaki, Timothy Tang, Neil A Shneider, James L Manley
An expanded GGGGCC hexanucleotide in C9ORF72 (C9) is the most frequent known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It has been proposed that expanded transcripts adopt G-quadruplex (G-Q) structures and associate with proteins, but whether this occurs and contributes to disease is unknown. Here we show first that the protein that predominantly associates with GGGGCC repeat RNA in vitro is the splicing factor hnRNP H, and that this interaction is linked to G-Q formation...
September 13, 2016: ELife
https://www.readbyqxmd.com/read/27595546/the-prevalent-deep-intronic-c-639-919-g-a-gla-mutation-causes-pseudoexon-activation-and-fabry-disease-by-abolishing-the-binding-of-hnrnpa1-and-hnrnp-a2-b1-to-a-splicing-silencer
#15
Bruno Palhais, Maja Dembic, Rugivan Sabaratnam, Kira S Nielsen, Thomas Koed Doktor, Gitte Hoffmann Bruun, Brage Storstein Andresen
Fabry disease is an X-linked recessive inborn disorder of the glycosphingolipid metabolism, caused by total or partial deficiency of the lysosomal α-galactosidase A enzyme due to mutations in the GLA gene. The prevalent c.639+919 G>A mutation in GLA leads to pathogenic insertion of a 57bp pseudoexon sequence from intron 4, which is responsible for the cardiac variant phenotype. In this study we investigate the splicing regulatory mechanism leading to GLA pseudoexon activation. Splicing analysis of GLA minigenes revealed that pseudoexon activation is influenced by cell-type...
August 27, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27501755/a-novel-role-for-the-nuclear-localization-signal-in-regulating-hnrnp-k-protein-stability-in%C3%A2-vivo
#16
Erica J Hutchins, Jamie L Belrose, Ben G Szaro
hnRNP K is a highly conserved nucleocytoplasmic shuttling protein, which associates with RNAs through synergistic binding via its three KH domains. hnRNP K is required for proper nuclear export and translational control of its mRNA targets, and these processes are controlled by hnRNP K's movement between subcellular compartments. Whereas the nuclear export and localization of hnRNP K that is associated with mRNP complexes has been well studied, the trafficking of hnRNP K that is unbound to mRNA has yet to be elucidated...
September 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27495811/the-arabidopsis-hnrnp-q-protein-lif2-and-the-prc1-subunit-lhp1-function-in-concert-to-regulate-the-transcription-of-stress-responsive-genes
#17
Anne Molitor, David Latrasse, Matthias Zytnicki, Philippe Andrey, Nicole Houba-Hérin, Mélanie Hachet, Christophe Battail, Stefania Del Prete, Adriana Alberti, Hadi Quesneville, Valerie Gaudin
LHP1-INTERACTING FACTOR2 (LIF2), a heterogeneous nuclear ribonucleoprotein involved in Arabidopsis thaliana cell fate and stress responses, interacts with LIKE HETEROCHROMATIN PROTEIN1 (LHP1), a Polycomb Repressive Complex1 (PRC1) subunit. To investigate LIF2-LHP1 functional interplay, we mapped their genome-wide distributions in wild-type, lif2, and lhp1 backgrounds, under standard and stress conditions. Interestingly, LHP1-targeted regions form local clusters, suggesting an underlying functional organization of the plant genome...
August 5, 2016: Plant Cell
https://www.readbyqxmd.com/read/27494769/cylindrospermopsin-effects-on-protein-profile-of-hepg2-cells
#18
Samuel Liebel, Sonia Regina Grötzner, Daniele Dietrich Moura Costa, Marco Antônio Ferreira Randi, Ciro Alberto de Oliveira Ribeiro, Francisco Filipak Neto
Human hepatoma cells (HepG2) were exposed to purified cylindrospermopsin (CYN), a potent toxicant for eukaryotic cells produced by several cyanobacteria. Exposure to 10 μg l(-1) of CYN for 24 h resulted in alteration of expression of 48 proteins, from which 26 were identified through mass spectrometry. Exposure to 100 μg l(-1) of CYN for 24 h affected nuclear area and actin filaments intensity, which can be associated with cell proliferation and toxicity. The proteins are implicated in different biological processes: protein folding, xenobiotic efflux, antioxidant defense, energy metabolism and cell anabolism, cell signaling, tumorigenic potential, and cytoskeleton structure...
September 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27277805/cholinergic-regulation-of-hnrnpa2-b1-translation-by-m1-muscarinic-receptors
#19
Benjamin Kolisnyk, Mohammed A Al-Onaizi, Jason Xu, Gustavo M Parfitt, Valeriy G Ostapchenko, Geula Hanin, Hermona Soreq, Marco A M Prado, Vania F Prado
UNLABELLED: Cholinergic vulnerability, characterized by loss of acetylcholine (ACh), is one of the hallmarks of Alzheimer's disease (AD). Previous work has suggested that decreased ACh activity in AD may contribute to pathological changes through global alterations in alternative splicing. This occurs, at least partially, via the regulation of the expression of a critical protein family in RNA processing, heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins. These proteins regulate several steps of RNA metabolism, including alternative splicing, RNA trafficking, miRNA export, and gene expression, providing multilevel surveillance in RNA functions...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27168114/sst2-translation-is-regulated-by-fgf2-via-an-hnrnp-a1-mediated-ires-dependent-mechanism
#20
Michael M Kunze, Fabienne Benz, Thilo F Brauß, Sebastian Lampe, Julia E Weigand, Johannes Braun, Florian M Richter, Ilka Wittig, Bernhard Brüne, Tobias Schmid
Translation is an energy-intensive process and tightly regulated. Generally, translation is initiated in a cap-dependent manner. Under stress conditions, typically found within the tumor microenvironment in association with e.g. nutrient deprivation or hypoxia, cap-dependent translation decreases, and alternative modes of translation initiation become more important. Specifically, internal ribosome entry sites (IRES) facilitate translation of specific mRNAs under otherwise translation-inhibitory conditions...
July 2016: Biochimica et Biophysica Acta
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