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transcription Cap binding protein

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https://www.readbyqxmd.com/read/28928453/molecular-characterization-of-emaraviruses-associated-with-pigeonpea-sterility-mosaic-disease
#1
Surender Kumar, B L Subbarao, Vipin Hallan
Sterility Mosaic Disease (SMD) of pigeonpea (Cajanus cajan (L.) Millspaugh) is a complex disease due to various factors including the presence of a mixed infection. Comparison of dsRNA profile and small RNA (sRNA) deep sequencing analysis of samples from three locations revealed the presence of Pigeonpea sterility mosaic virus-I and II (PPSMV-I and II) from Chevella and only PPSMV-II from Bengaluru and Coimbatore. PPSMV-I genome consisted of four while PPSMV-II encompassed six RNAs. The two viruses have modest sequence homology between their corresponding RNA 1-4 encoding RdRp, glycoprotein precursor, nucleocapsid and movement proteins and the corresponding orthologs of other emaraviruses...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904350/tia1-dependent-regulation-of-mrna-subcellular-location-and-translation-controls-p53-expression-in-b-cells
#2
Manuel D Díaz-Muñoz, Vladimir Yu Kiselev, Nicolas Le Novère, Tomaz Curk, Jernej Ule, Martin Turner
Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28839261/structural-basis-for-therapeutic-inhibition-of-influenza-a-polymerase-pb2-subunit
#3
Xiaolei Ma, Lili Xie, Charles Wartchow, Robert Warne, Yongjin Xu, Alexey Rivkin, David Tully, Steven Shia, Kyoko Uehara, Dianna M Baldwin, Gladys Muiru, Weidong Zhong, Isabel Zaror, Dirksen E Bussiere, Vincent H J Leonard
Influenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the viral heterotrimeric RNA polymerase binds the cap structure of cellular pre-mRNA to promote its cleavage by the PA subunit. The resulting 11-13 capped oligomer is used by the PB1 polymerase subunit to initiate transcription of viral proteins. VX-787 is an inhibitor of the influenza A virus pre-mRNA cap-binding protein PB2. This clinical stage compound was shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821580/cap-independent-translation-ensures-mtor-expression-and-function-upon-protein-synthesis-inhibition
#4
Ana Marques-Ramos, Marco M Candeias, Juliane Menezes, Rafaela Lacerda, Margaret Willcocks, Alexandre Teixeira, Nicolas Locker, Luisa Romao
The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that human mTOR transcript can be translated in a cap-independent manner, and that its 5' untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit...
August 18, 2017: RNA
https://www.readbyqxmd.com/read/28791367/molecular-mechanisms-of-breast-cancer-metastasis-by-gene-expression-profile-analysis
#5
Tianying Zheng, Aijun Wang, Dongyan Hu, Yonggang Wang
Metastasis is the main cause of breast cancer‑related mortalities. The present study aimed to uncover the relevant molecular mechanisms of breast cancer metastasis and to explore potential biomarkers that may be used for prognosis. Expression profile microarray data GSE8977, which contained 22 stroma samples (15 were from normal breast and 7 were from invasive ductal carcinoma tumor samples), were obtained from the Gene Expression Omnibus database. Following data preprocessing, differentially expressed genes (DEGs) were selected based on analyses conducted using the linear models for microarray analysis package from R and Bioconductor software...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28771520/variations-of-five-eif4e-genes-across-cassava-accessions-exhibiting-tolerant-and-susceptible-responses-to-cassava-brown-streak-disease
#6
Shanshan Shi, Xiuchun Zhang, M Alejandra Mandel, Peng Zhang, Yuliang Zhang, Morag Ferguson, Teddy Amuge, Steve Rounsley, Zhixin Liu, Zhongguo Xiong
Cassava (Manihot esculenta) is an important tropical subsistence crop that is severely affected by cassava brown streak disease (CBSD) in East Africa. The disease is caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Both have a (+)-sense single-stranded RNA genome with a 5' covalently-linked viral protein, which functionally resembles the cap structure of mRNA, binds to eukaryotic translation initiation factor 4E (eIF4E) or its analogues, and then enable the translation of viral genomic RNA in host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28747503/identification-of-vaccinia-virus-replisome-and-transcriptome-proteins-by-isolation-of-proteins-on-nascent-dna-coupled-with-mass-spectrometry
#7
Tatiana G Senkevich, George C Katsafanas, Andrea Weisberg, Lisa R Olano, Bernard Moss
Poxviruses replicate within the cytoplasm and encode proteins for DNA and mRNA synthesis. To investigate poxvirus replication and transcription from a new perspective, we incorporated 5-ethynyl-2'-deoxyuridine (EdU) into nascent DNA in cells infected with vaccinia virus (VACV). The EdU-labeled DNA was conjugated to fluor- or biotin-azide and visualized by confocal, superresolution, and transmission electron microscopy. Nuclear labeling decreased dramatically after infection, accompanied by intense labeling of cytoplasmic foci...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746365/cbp80-is-needed-for-the-expression-of-pirna-components-and-pirnas
#8
Ravish Rashpa, Paula Vazquez-Pianzola, Martino Colombo, Greco Hernandez, Dirk Beuchle, Fabienne Berger, Stephan Peischl, Rémy Bruggmann, Beat Suter
Cap binding protein 80 (Cbp80) is the larger subunit of the nuclear cap-binding complex (nCBC), which is known to play important roles in nuclear mRNA processing, export, stability and quality control events. Reducing Cbp80 mRNA levels in the female germline revealed that Cbp80 is also involved in defending the germline against transposable elements. Combining such knockdown experiments with large scale sequencing of small RNAs further showed that Cbp80 is involved in the initial biogenesis of piRNAs as well as in the secondary biogenesis pathway, the ping-pong amplification cycle...
2017: PloS One
https://www.readbyqxmd.com/read/28698298/gigyf1-2-proteins-use-auxiliary-sequences-to-selectively-bind-to-4ehp-and-repress-target-mrna-expression
#9
Daniel Peter, Ramona Weber, Felix Sandmeir, Lara Wohlbold, Sigrun Helms, Praveen Bawankar, Eugene Valkov, Cátia Igreja, Elisa Izaurralde
The eIF4E homologous protein (4EHP) is thought to repress translation by competing with eIF4E for binding to the 5' cap structure of specific mRNAs to which it is recruited through interactions with various proteins, including the GRB10-interacting GYF (glycine-tyrosine-phenylalanine domain) proteins 1 and 2 (GIGYF1/2). Despite its similarity to eIF4E, 4EHP does not interact with eIF4G and therefore fails to initiate translation. In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for 4EHP...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28620032/a-moving-target-structure-and-disorder-in-pursuit-of-myc-inhibitors
#10
REVIEW
Richard Bayliss, Selena G Burgess, Eoin Leen, Mark W Richards
The Myc proteins comprise a family of ubiquitous regulators of gene expression implicated in over half of all human cancers. They interact with a large number of other proteins, such as transcription factors, chromatin-modifying enzymes and kinases. Remarkably, few of these interactions have been characterized structurally. This is at least in part due to the intrinsically disordered nature of Myc proteins, which adopt a defined conformation only in the presence of binding partners. Owing to this behaviour, crystallographic studies on Myc proteins have been limited to short fragments in complex with other proteins...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28601225/impact-of-rna-modifications-and-rna-modifying-enzymes-on-eukaryotic-ribonucleases
#11
Guillaume F Chanfreau
Constitutive and regulated turnover of RNAs is necessary to eliminate aberrant RNA molecules and control the level of specific mRNAs to maintain homeostasis or to respond to signals in living cells. Modifications of nucleosides in specific RNAs are important in modulating the functions of these transcripts, but they can also dramatically impact their fate and turnover. This chapter will review how RNA modifications impact the activities of ribonucleases that target these RNAs for degradation or cleavage, focusing more particularly on tRNAs and mRNAs in eukaryotic cells...
2017: Enzymes
https://www.readbyqxmd.com/read/28522457/structure-of-eif4e-in-complex-with-an-eif4g-peptide-supports-a-universal-bipartite-binding-mode-for-protein-translation
#12
Manuel Miras, Verónica Truniger, Cristina Silva, Núria Verdaguer, Miguel A Aranda, Jordi Querol-Audí
The association-dissociation of the cap-binding protein eukaryotic translation initiation factor 4E (eIF4E) with eIF4G is a key control step in eukaryotic translation. The paradigm on the eIF4E-eIF4G interaction states that eIF4G binds to the dorsal surface of eIF4E through a single canonical alpha-helical motif, while metazoan eIF4E-binding proteins (m4E-BPs) advantageously compete against eIF4G via bimodal interactions involving this canonical motif and a second noncanonical motif of the eIF4E surface. Metazoan eIF4Gs share this extended binding interface with m4E-BPs, with significant implications on the understanding of translation regulation and the design of therapeutic molecules...
July 2017: Plant Physiology
https://www.readbyqxmd.com/read/28515298/crimean-congo-hemorrhagic-fever-virus-nucleocapsid-protein-augments-mrna-translation
#13
Subbiah Jeeva, Erdong Cheng, Safder S Ganaie, Mohammad A Mir
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap...
August 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#14
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454255/mir-219-5p-suppresses-the-proliferation-and-invasion-of-colorectal-cancer-cells-by-targeting-calcyphosin
#15
Quhui Wang, Lirong Zhu, Yasu Jiang, Junfei Xu, Feiran Wang, Zhixian He
MicroRNAs (miRNAs) are small non-coding RNAs involved in an array of biological processes, and their dysregulation is associated with tumor development and progression. One such miRNA, miR-219-5p, is abnormally expressed in patients with colorectal cancer (CRC). In the present study, reverse transcription-quantitative polymerase chain reaction was performed to measure miR-219-5p expression in cells from both CRC tumors, and surrounding healthy tissue. MTT and invasion assays were used to determine the role of miR-219-5p in regulating CRC cell proliferation and invasion, respectively...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28378569/porcine-circovirus-type-2-capsid-protein-induces-unfolded-protein-response-with-subsequent-activation-of-apoptosis
#16
Ying-Shan Zhou, Yuan-Xing Gu, Bao-Zhu Qi, Yi-Kai Zhang, Xiao-Liang Li, Wei-Huan Fang
Porcine circovirus type 2 (PCV2) has recently been reported to elicit the unfolded protein response (UPR) via activation of the PERK/eIF2α (RNA-activated protein kinase-like endoplasmic reticulum (ER) kinase/eukaryotic initiation factor 2α) pathway. This study attempted to examine which viral protein might be involved in inducing UPR and whether this cellular event would lead to apoptosis of the cells expressing the viral protein. By transient expression, we found that both replicase (Rep) and capsid (Cap) proteins of PCV2 could induce ER stress as shown by increased phosphorylation of PERK with subsequent activation of the eIF2α-ATF4 (activating transcription factor 4)-CHOP (CCAAT/enhancer-binding protein homologous protein) axis...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28329686/demethylated-hsatii-dna-and-hsatii-rna-foci-sequester-prc1-and-mecp2-into-cancer-specific-nuclear-bodies
#17
Lisa L Hall, Meg Byron, Dawn M Carone, Troy W Whitfield, Gayle P Pouliot, Andrew Fischer, Peter Jones, Jeanne B Lawrence
This study reveals that high-copy satellite II (HSATII) sequences in the human genome can bind and impact distribution of chromatin regulatory proteins and that this goes awry in cancer. In many cancers, master regulatory proteins form two types of cancer-specific nuclear bodies, caused by locus-specific deregulation of HSATII. DNA demethylation at the 1q12 mega-satellite, common in cancer, causes PRC1 aggregation into prominent Cancer-Associated Polycomb (CAP) bodies. These loci remain silent, whereas HSATII loci with reduced PRC1 become derepressed, reflecting imbalanced distribution of UbH2A on these and other PcG-regulated loci...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28325843/a-biochemical-framework-for-eif4e-dependent-mrna-export-and-nuclear-recycling-of-the-export-machinery
#18
Laurent Volpon, Biljana Culjkovic-Kraljacic, Hye Seon Sohn, Alexis Blanchet-Cohen, Michael J Osborne, Katherine L B Borden
The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end...
June 2017: RNA
https://www.readbyqxmd.com/read/28297668/mutually-exclusive-cbc-containing-complexes-contribute-to-rna-fate
#19
Simone Giacometti, Nour El Houda Benbahouche, Michal Domanski, Marie-Cécile Robert, Nicola Meola, Michal Lubas, Jakob Bukenborg, Jens S Andersen, Wiebke M Schulze, Celine Verheggen, Grzegorz Kudla, Torben Heick Jensen, Edouard Bertrand
The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3'-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3'-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28287067/translational-control-of-mrnas-by-3-untranslated-region-binding-proteins
#20
Akio Yamashita, Osamu Takeuchi
Eukaryotic gene expression is precisely regulated at all points between transcription and translation. In this review, we focus on translational control mediated by the 3'-untranslated regions (UTRs) of mRNAs. mRNA 3'-UTRs contain cis-acting elements that function in the regulation of protein translation or mRNA decay. Each RNA binding protein that binds to these cis-acting elements regulates mRNA translation via various mechanisms targeting the mRNA cap structure, the eukaryotic initiation factor 4E (eIF4E)-eIF4G complex, ribosomes, and the poly (A) tail...
April 2017: BMB Reports
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