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RNA binding proteins

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https://www.readbyqxmd.com/read/28437444/transcriptional-bursting-in-drosophila-development-stochastic-dynamics-of-eve-stripe-2-expression
#1
David M Holloway, Alexander V Spirov
Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first seen in the 7-stripe spatial expression patterns of the pair-rule genes, which regulate downstream genes determining specific segment identities. Regulation of pair-rule expression has been extensively studied for the even-skipped (eve) gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated the stochastic nature of this process, with 'bursts' in the number of RNA transcripts being made over time. We developed a stochastic model of the spatial and temporal expression of eve stripe 2 (binding by transcriptional activators (Bicoid and Hunchback proteins) and repressors (Giant and Krüppel proteins), transcriptional initiation and termination; with all rate parameters constrained by features of the experimental data) in order to analyze the noisy experimental time series and test hypotheses for how eve transcription is regulated...
2017: PloS One
https://www.readbyqxmd.com/read/28437166/virus-like-particles-of-mrna-with-artificial-minimal-coat-proteins-particle-formation-stability-and-transfection-efficiency
#2
Shehrazade Jekhmane, Rob de Haas, Omar Paulino da Silva Filho, Alexander H van Asbeck, Marco Emanuele Favretto, Armando Hernandez Garcia, Roland Brock, Renko de Vries
RNA has enormous potential as a therapeutic, yet, the successful application depends on efficient delivery strategies. In this study, we demonstrate that a designed artificial viral coat protein, which self-assembles with DNA to form rod-shaped virus-like particles (VLPs), also encapsulates and protects mRNA encoding enhanced green fluorescent protein (EGFP) and luciferase, and yields cellular expression of these proteins. The artificial viral coat protein consists of an oligolysine (K12) for binding to the oligonucleotide, a silk protein-like midblock S10 = (GAGAGAGQ)10 that self-assembles into stiff rods, and a long hydrophilic random coil block C that shields the nucleic acid cargo from its environment...
February 21, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28436990/tcrp1-promotes-nih-3t3-cell-transformation-by-over-activating-pdk1-and-akt1
#3
C Wang, H Liu, Q Qiu, Z Zhang, Y Gu, Z He
Tongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our precious studies demonstrated that TCRP1 was involving in chemotherapy and radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian cancer cells. In this study, we showed that TCRP1 overexpression promotes cell transformation and tumorigenesis through hyperphosphorylation of the oncogenic kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1-mediated cell transformation...
April 24, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#4
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
April 24, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#5
P von Morgen, K Burdova, T G Flower, N J O'Reilly, S J Boulton, S J Smerdon, L Macurek, Z Hořejší
The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28435471/nucleolin-targeted-extracellular-vesicles-as-a-versatile-platform-for-biologics-delivery-to-breast-cancer
#6
Yayu Wang, Xiaojia Chen, Baoqing Tian, Jiafan Liu, Li Yang, Lilan Zeng, Tianfen Chen, An Hong, Xiaogang Wang
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28435090/trinucleotide-repeat-expanded-and-normal-dmpk-transcripts-contain-unusually-long-poly-a-tails-despite-differential-nuclear-residence
#7
Anke E E G Gudde, Ingeborg D G van Kessel, Laurène M André, Bé Wieringa, Derick G Wansink
In yeast and higher eukaryotes nuclear retention of transcripts may serve in control over RNA decay, nucleocytoplasmic transport and premature cytoplasmic appearance of mRNAs. Hyperadenylation of RNA is known to be associated with nuclear retention, but the cause-consequence relationship between hyperadenylation and regulation of RNA nuclear export is still unclear. We compared polyadenylation status between normal and expanded DMPK transcripts in muscle cells and tissues derived from unaffected individuals and patients with myotonic dystrophy type 1 (DM1)...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28434996/effect-of-heparin-and-heparan-sulphate-on-open-promoter-complex-formation-for-a-simple-tandem-gene-model-using-ex-situ-atomic-force-microscopy
#8
Oliver Chammas, William A Bonass, Neil H Thomson
The influence of heparin and heparan sulphate (HepS) on the appearance and analysis of open promoter complex (RPo) formation by E. coli RNA polymerase (RNAP) holoenzyme (σ(70)RNAP) on linear DNA using ex-situ imaging by atomic force microscopy (AFM) has been investigated. Introducing heparin or HepS into the reaction mix significantly reduces non-specific interactions of the σ(70)RNAP and RNAP after RPo formation allowing for better interpretation of complexes shown within AFM images, particularly on DNA templates containing more than one promoter...
April 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28434858/stem-cell-intrinsic-seven-up-triggered-temporal-factor-gradients-diversify-intermediate-neural-progenitors
#9
Qingzhong Ren, Ching-Po Yang, Zhiyong Liu, Ken Sugino, Kent Mok, Yisheng He, Masayoshi Ito, Aljoscha Nern, Hideo Otsuna, Tzumin Lee
Building a sizable, complex brain requires both cellular expansion and diversification. One mechanism to achieve these goals is production of multiple transiently amplifying intermediate neural progenitors (INPs) from a single neural stem cell. Like mammalian neural stem cells, Drosophila type II neuroblasts utilize INPs to produce neurons and glia. Within a given lineage, the consecutively born INPs produce morphologically distinct progeny, presumably due to differential inheritance of temporal factors. To uncover the underlying temporal fating mechanisms, we profiled type II neuroblasts' transcriptome across time...
April 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28434825/rna-binding-proteins-in-human-oogenesis-balancing-differentiation-and-self-renewal-in-the-female-fetal-germline
#10
Roseanne Rosario, Andrew J Childs, Richard A Anderson
Primordial germ cells undergo three significant processes on their path to becoming primary oocytes: the initiation of meiosis, the formation and breakdown of germ cell nests, and the assembly of single oocytes into primordial follicles. However at the onset of meiosis, the germ cell becomes transcriptionally silenced. Consequently translational control of pre-stored mRNAs plays a central role in coordinating gene expression throughout the remainder of oogenesis; RNA binding proteins are key to this regulation...
April 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28434803/genetic-dissection-of-the-planarian-reproductive-system-through-characterization-of-schmidtea-mediterranea-cpeb-homologs
#11
Labib Rouhana, Junichi Tasaki, Amir Saberi, Phillip A Newmark
Cytoplasmic polyadenylation is a mechanism of mRNA regulation prevalent in metazoan germ cells; it is largely dependent on Cytoplasmic Polyadenylation Element Binding proteins (CPEBs). Two CPEB homologs were identified in the planarian Schmidtea mediterranea. Smed-CPEB1 is expressed in ovaries and yolk glands of sexually mature planarians, and required for oocyte and yolk gland development. In contrast, Smed-CPEB2 is expressed in the testes and the central nervous system; its function is required for spermatogenesis as well as non-autonomously for development of ovaries and accessory reproductive organs...
April 20, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28433711/mdh2-is-an-rna-binding-protein-involved-in-downregulation-of-sodium-channel-scn1a-expression-under-seizure-condition
#12
Yong-Hong Chen, Shu-Jing Liu, Mei-Mei Gao, Tao Zeng, Guo-Wang Lin, Na-Na Tan, Hui-Ling Tang, Ping Lu, Tao Su, Wei-Wen Sun, Long-Chang Xie, Yong-Hong Yi, Yue-Sheng Long
Voltage-gated sodium channel α-subunit type I (NaV1.1, encoded by SCN1A gene) plays a critical role in the excitability of brain. Downregulation of SCN1A expression is associated with epilepsy, a common neurological disorder characterized by recurrent seizures. Here we reveal a novel role of malate dehydrogenase 2 (MDH2) in the posttanscriptional regulation of SCN1A expression under seizure condition. We identified that MDH2 was an RNA binding protein that could bind two of the four conserved regions in the 3' UTRs of SCN1A...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28433538/the-ns1-protein-from-influenza-virus-stimulates-translation-initiation-by-enhancing-ribosome-recruitment-to-mrnas
#13
Baptiste Panthu, Olivier Terrier, Coralie Carron, Aurélien Traversier, Antoine Corbin, Laurent Balvay, Bruno Lina, Manuel Rosa-Calatrava, Théophile Ohlmann
The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Amongst these functions, NS1 was shown to be involved both in the control of viral and cellular translation; however the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses IRESes (DCV and CrPV), suggesting a role at the level of translation initiation...
April 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28432618/the-identification-of-key-genes-and-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis-of-high-throughput-data
#14
Chaoyang Zhang, Li Peng, Yaqin Zhang, Zhaoyang Liu, Wenling Li, Shilian Chen, Guancheng Li
Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28432356/a-role-of-human-rnase-p-subunits-rpp29-and-rpp21-in-homology-directed-repair-of-double-strand-breaks
#15
Enas R Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432336/structure-function-analysis-of-the-dna-binding-domain-of-a-transmembrane-transcriptional-activator
#16
Andreas Schlundt, Sophie Buchner, Robert Janowski, Thomas Heydenreich, Ralf Heermann, Jürgen Lassak, Arie Geerlof, Ralf Stehle, Dierk Niessing, Kirsten Jung, Michael Sattler
The transmembrane DNA-binding protein CadC of E. coli, a representative of the ToxR-like receptor family, combines input and effector domains for signal sensing and transcriptional activation, respectively, in a single protein, thus representing one of the simplest signalling systems. At acidic pH in a lysine-rich environment, CadC activates the transcription of the cadBA operon through recruitment of the RNA polymerase (RNAP) to the two cadBA promoter sites, Cad1 and Cad2, which are directly bound by CadC...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431495/iron-regulated-small-rna-expression-as-neisseria-gonorrhoeae-fa-1090-transitions-into-stationary-phase-growth
#17
Lydgia A Jackson, Michael Day, Jennie Allen, Edgar Scott, David W Dyer
BACKGROUND: For most pathogens, iron (Fe) homeostasis is crucial for maintenance within the host and the ability to cause disease. The primary transcriptional regulator that controls intracellular Fe levels is the Fur (ferric uptake regulator) protein, which exerts its action on transcription by binding to a promoter-proximal sequence termed the Fur box. Fur-regulated transcriptional responses are often fine-tuned at the post-transcriptional level through the action of small regulatory RNAs (sRNAs)...
April 21, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#18
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#19
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431232/genome-wide-mapping-of-drosha-cleavage-sites-on-primary-micrornas-and-noncanonical-substrates
#20
Baekgyu Kim, Kyowon Jeong, V Narry Kim
MicroRNA (miRNA) maturation is initiated by DROSHA, a double-stranded RNA (dsRNA)-specific RNase III enzyme. By cleaving primary miRNAs (pri-miRNAs) at specific positions, DROSHA serves as a main determinant of miRNA sequences and a highly selective gatekeeper for the canonical miRNA pathway. However, the sites of DROSHA-mediated processing have not been annotated, and it remains unclear to what extent DROSHA functions outside the miRNA pathway. Here, we establish a protocol termed "formaldehyde crosslinking, immunoprecipitation, and sequencing (fCLIP-seq)," which allows identification of DROSHA cleavage sites at single-nucleotide resolution...
April 20, 2017: Molecular Cell
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