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RNA binding proteins

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https://www.readbyqxmd.com/read/29792818/substrate-induced-formation-of-ribosomal-decoding-center-for-accurate-and-rapid-genetic-code-translation
#1
Michael Y Pavlov, Måns Ehrenberg
Accurate translation of genetic information is crucial for synthesis of functional proteins in all organisms. We use recent experimental data to discuss how induced fit affects accuracy of initial codon selection on the ribosome by aminoacyl transfer RNA in ternary complex ( T3 ) with elongation factor Tu (EF-Tu) and guanosine-5'-triphosphate (GTP). We define actual accuracy ([Formula: see text]) of a particular protein synthesis system as its current accuracy and the effective selectivity ([Formula: see text]) as [Formula: see text] in the limit of zero ribosomal binding affinity for T3 ...
May 20, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29792216/hiv-1-tat-phosphorylation-on-ser-16-residue-modulates-hiv-1-transcription
#2
Andrey Ivanov, Xionghao Lin, Tatiana Ammosova, Andrey V Ilatovskiy, Namita Kumari, Hatajai Lassiter, Nowah Afangbedji, Xiaomei Niu, Michael G Petukhov, Sergei Nekhai
BACKGROUND: HIV-1 transcription activator protein Tat is phosphorylated in vitro by CDK2 and DNA-PK on Ser-16 residue and by PKR on Tat Ser-46 residue. Here we analyzed Tat phosphorylation in cultured cells and its functionality. RESULTS: Mass spectrometry analysis showed primarily Tat Ser-16 phosphorylation in cultured cells. In vitro, CDK2/cyclin E predominantly phosphorylated Tat Ser-16 and PKR-Tat Ser-46. Alanine mutations of either Ser-16 or Ser-46 decreased overall Tat phosphorylation...
May 23, 2018: Retrovirology
https://www.readbyqxmd.com/read/29791798/non-natural-linker-configuration-in-2-6-dipeptidyl-anthraquinones-enhances-the-inhibition-of-tar-rna-binding-annealing-activities-by-hiv-1-nc-and-tat-proteins
#3
Alice Sosic, Irene Saccone, Caterina Carraro, Thomas Kenderdine, Elia Gamba, Giuseppe Caliendo, Angela Corvino, Ferdinando Fiorino, Paola DiVaio, Elisa Magli, Elisa Perissutti, Vincenzo Santagada, Beatrice Severino, Valentina Spada, Daniele Fabris, Francesco Frecentese, Barbara Gatto
The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of antiretrovirals by virtue of its well-characterized chaperone activities, which play pivotal roles in essential steps of the viral life cycle. Our ongoing search for candidates able to impair NC binding/annealing activities led to the identification of peptidyl-anthraquinones as a promising class of nucleic acid ligands. Seeking to elucidate the inhibition determinants and increase the potency of this class of compounds, we have now explored the effects of chirality in the linker connecting the planar nucleus to the basic side chains...
May 23, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29791316/roles-of-the-exon-junction-complex-components-in-the-central-nervous-system-a-mini-review
#4
Katarzyna Bartkowska, Beata Tepper, Kris Turlejski, Ruzanna L Djavadian
The exon junction complex (EJC) consists of four core proteins: Magoh, RNA-binding motif 8A (Rbm8a, also known as Y14), eukaryotic initiation factor 4A3 (eIF4A3, also known as DDX48), and metastatic lymph node 51 (MLN51, also known as Casc3 or Barentsz), which are involved in the regulation of many processes occurring between gene transcription and protein translation. Its main role is to assemble into spliceosomes at the exon-exon junction of mRNA during splicing. It is, therefore, a range of functions concerning post-splicing events such as mRNA translocation, translation, and nonsense-mediated mRNA decay (NMD)...
May 23, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29791134/identification-of-yth-domain-containing-proteins-as-the-readers-for-n1-methyladenosine-in-rna
#5
Xiaoxia Dai, Tianlu Wang, Gwendolyn Gonzalez, Yinsheng Wang
N1-methyladenosine (m1 A) is an important post-transcriptional modification in RNA; however, the exact biological role of m1 A remains to be determined. By employing a quantitative proteomics method, we identified multiple putative protein readers of m1 A in RNA, including several YTH domain family proteins. We showed that YTHDF1-3 and YTHDC1, but not YTHDC2, could bind directly to m1 A in RNA. We also found that Trp432 in YTHDF2, a conserved residue in the hydrophobic pocket of the YTH domain that is necessary for its binding to N6 -methyladenosine (m6 A), is required for its recognition of m1 A...
May 25, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29790987/structural-accommodations-accompanying-splicing-of-a-group-ii-intron-rnp
#6
Xiaolong Dong, Srivathsan Ranganathan, Guosheng Qu, Carol Lyn Piazza, Marlene Belfort
Group II introns, the putative progenitors of spliceosomal introns and retrotransposons, are ribozymes that are capable of self-splicing and DNA invasion. In the cell, group II introns form ribonucleoprotein (RNP) complexes with an intron-encoded protein, which is essential to folding, splicing and retromobility of the intron. To understand the structural accommodations underlying splicing, in preparation for retromobility, we probed the endogenously expressed Lactococcus lactis Ll.LtrB group II intron RNP using SHAPE...
May 22, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29790588/the-lncrna-casc9-and-rna-binding-protein-hnrnpl-form-a-complex-and-co-regulate-genes-linked-to-akt-signaling
#7
Marcel Klingenberg, Matthias Groß, Ashish Goyal, Maria Polycarpou-Schwarz, Thilo Miersch, Anne-Sophie Ernst, Jörg Leupold, Nitin Patil, Uwe Warnken, Heike Allgayer, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sven Diederichs
The identification of viability-associated long non-coding RNAs (lncRNA) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied the first RNAi screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected CASC9 (Cancer Susceptibility 9) due to the strength of its phenotype, expression, and upregulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by CRISPR interference, single siRNA- and siPOOL-mediated depletion of CASC9...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29790280/cas9-versus-cas12a-cpf1-structure-function-comparisons-and-implications-for-genome-editing
#8
REVIEW
Daan C Swarts, Martin Jinek
Cas9 and Cas12a are multidomain CRISPR-associated nucleases that can be programmed with a guide RNA to bind and cleave complementary DNA targets. The guide RNA sequence can be varied, making these effector enzymes versatile tools for genome editing and gene regulation applications. While Cas9 is currently the best-characterized and most widely used nuclease for such purposes, Cas12a (previously named Cpf1) has recently emerged as an alternative for Cas9. Cas9 and Cas12a have distinct evolutionary origins and exhibit different structural architectures, resulting in distinct molecular mechanisms...
May 22, 2018: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29789783/mir-142-5p-in-bone-marrow-derived-mesenchymal-stem-cells-promotes-osteoporosis-involving-targeting-adhesion-molecule-vcam-1-and-inhibiting-cell-migration
#9
Zhaowei Teng, Xueguan Xie, Yun Zhu, Jianping Liu, Xingbo Hu, Qiang Na, Xiongwen Zhang, Guojun Wei, Shen Xu, Yugang Liu, Xiguang Zhang, Cory J Xian
Osteoporosis is a systemic bone metabolic disease that is highly prevalent in the elderly population, particularly in postmenopausal women, which results in enhanced bone fragility and an increased susceptibility to fractures. However, the underlying molecular pathogenesis mechanisms still remain to be further elucidated. In this study, in a rat ovariectomy- (OVX-) induced postmenopausal osteoporosis model, aberrant expression of a microRNA miR-142-5p and vascular cell adhesion molecule 1 (VCAM-1) was found by RNA sequencing analysis and qRT-PCR...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29789713/upregulation-of-the-long-noncoding-rna-foxd2-as1-promotes-carcinogenesis-by-epigenetically-silencing-ephb3-through-ezh2-and-lsd1-and-predicts-poor-prognosis-in-gastric-cancer
#10
Tong-Peng Xu, Wen-Yu Wang, Pei Ma, You Shuai, Kun Zhao, Yan-Fen Wang, Wei Li, Rui Xia, Wen-Ming Chen, Er-Bao Zhang, Yong-Qian Shu
Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1 expression...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789685/s100a4-protects-mice-from-high-fat-diet-induced-obesity-and-inflammation
#11
Shasha Hou, Ying Jiao, Qi Yuan, Junfeng Zhai, Tian Tian, Kaiji Sun, Zhinan Chen, Zhenlong Wu, Jinhua Zhang
As a member from S100 calcium-binding protein family, S100A4 is ubiquitous and elevated in tumor progression and metastasis, but its role in regulating obesity has not been well characterized. In this study, we showed that S100A4 was mainly expressed by stromal cells in adipose tissue and the S100A4 level in adipose tissue was decreased after high-fat diet (HFD). S100A4 deficient mice exhibited aggravated symptoms of obesity and suppressed insulin signaling after 12 weeks of HFD. Aggravated obesity in S100A4 deficient mice were found to be positively correlated with higher inflammatory status of the liver...
May 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29789616/rbfox1-mbnl1-competition-for-ccug-rna-repeats-binding-contributes-to-myotonic-dystrophy-type-1-type-2-differences
#12
Chantal Sellier, Estefanía Cerro-Herreros, Markus Blatter, Fernande Freyermuth, Angeline Gaucherot, Frank Ruffenach, Partha Sarkar, Jack Puymirat, Bjarne Udd, John W Day, Giovanni Meola, Guillaume Bassez, Harutoshi Fujimura, Masanori P Takahashi, Benedikt Schoser, Denis Furling, Ruben Artero, Frédéric H T Allain, Beatriz Llamusi, Nicolas Charlet-Berguerand
Myotonic dystrophy type 1 and type 2 (DM1, DM2) are caused by expansions of CTG and CCTG repeats, respectively. RNAs containing expanded CUG or CCUG repeats interfere with the metabolism of other RNAs through titration of the Muscleblind-like (MBNL) RNA binding proteins. DM2 follows a more favorable clinical course than DM1, suggesting that specific modifiers may modulate DM severity. Here, we report that the rbFOX1 RNA binding protein binds to expanded CCUG RNA repeats, but not to expanded CUG RNA repeats...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789581/intron-retention-and-nuclear-loss-of-sfpq-are-molecular-hallmarks-of-als
#13
Raphaelle Luisier, Giulia E Tyzack, Claire E Hall, Jamie S Mitchell, Helen Devine, Doaa M Taha, Bilal Malik, Ione Meyer, Linda Greensmith, Jia Newcombe, Jernej Ule, Nicholas M Luscombe, Rickie Patani
Mutations causing amyotrophic lateral sclerosis (ALS) strongly implicate ubiquitously expressed regulators of RNA processing. To understand the molecular impact of ALS-causing mutations on neuronal development and disease, we analysed transcriptomes during in vitro differentiation of motor neurons (MNs) from human control and patient-specific VCP mutant induced-pluripotent stem cells (iPSCs). We identify increased intron retention (IR) as a dominant feature of the splicing programme during early neural differentiation...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789508/dual-effects-of-metformin-on-adipogenic-differentiation-of-3t3-l1-preadipocyte-in-ampk-dependent-and-independent-manners
#14
Dian Chen, Ying Wang, Kaikai Wu, Xingya Wang
Metformin has been reported to have body weight lowering effects while treating type 2 diabetes. However, limited studies examined the effects of metformin on adipogenesis in vitro, and available data are inconclusive and contradictory. In this study, we examined the effects of a variety of concentrations of metformin on adipocyte differentiation of 3T3-L1 preadipocytes and found metformin exhibits a dual effect on adipogenesis. Metformin at lower concentrations (1.25⁻2.5 mM) significantly induced adipogenesis while at higher concentrations (5⁻10 mM) metformin significantly inhibited adipogenesis in 3T3-L1 cells...
May 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29789295/integration-of-protein-phosphorylation-acetylation-and-methylation-data-sets-to-outline-lung-cancer-signaling-networks
#15
Mark Grimes, Benjamin Hall, Lauren Foltz, Tyler Levy, Klarisa Rikova, Jeremiah Gaiser, William Cook, Ekaterina Smirnova, Travis Wheeler, Neil R Clark, Alexander Lachmann, Bin Zhang, Peter Hornbeck, Avi Ma'ayan, Michael Comb
Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs...
May 22, 2018: Science Signaling
https://www.readbyqxmd.com/read/29788176/cooperative-binding-of-apiap2-transcription-factors-is-crucial-for-the-expression-of-virulence-genes-in-toxoplasma-gondii
#16
Kevin M Lesage, Ludovic Huot, Thomas Mouveaux, Flavie Courjol, Jean-Michel Saliou, Mathieu Gissot
Toxoplasma gondii virulence depends on the expression of factors packed into specific organelles such as rhoptry and microneme. Although virulence factor expression is tightly regulated, the molecular mechanisms controlling their regulation remain poorly understood. ApiAP2 are a family of conserved transcription factors (TFs) that play an important role in regulating gene expression in apicomplexan parasites. TgAP2XI-5 is able to bind to transcriptionally active promoters of genes expressed during the S/M phase of the cell cycle, such as virulence genes (rhoptries and micronemes genes)...
May 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29787985/rna-binding-protein-lin28b-confers-gastric-cancer-cells-stemness-via-directly-binding-to-nrp-1
#17
Xiaocong Wang, Huihua Hu, Hebo Liu
This work aims to explore the roles and related mechanisms of RNA binding protein Lin28B in gastric cancer cells stemness. We found that Lin28B expression was negatively correlated with the overall survival (OS) of gastric cancer patients, and significantly increased in gastric cancer cells compared with that in gastric epithelial cells. Lin28B overexpression increased spheroid formation, expression of gastric cancer stemness-related markers, and decreased cisplatin sensitivity in gastric cancer cells. Mechanistically, Lin28B could directly bind to NRP-1 3'UTR, thus increasing NRP-1 mRNA stability and expression, and activate the downstream Wnt/β-catenin signaling...
May 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29787246/investigation-of-solvent-hydron-exchange-in-the-reaction-catalyzed-by-the-antibiotic-resistance-protein-cfr
#18
Matthew R Bauerle, Tyler L Grove, Squire J Booker
Cfr is a radical S-adenosylmethionine (RS) methylase that appends methyl groups to C8 and C2 of adenosine 2503 in 23S ribosomal RNA. Methylation of C8 confers resistance to several classes of antibiotics that bind in or near the peptidyl transferase center of the bacterial ribosome, including the synthetic antibiotic linezolid. The Cfr reaction requires the action of five conserved cysteines, three of which ligate a required [4Fe-4S] cluster cofactor. The two remaining cysteines play a more intricate role in the reaction, one of which (Cys338) becoming transiently methylated during catalysis...
May 22, 2018: Biochemistry
https://www.readbyqxmd.com/read/29785964/mechanism-of-selective-recruitment-of-rna-polymerases-ii-and-iii-to-snrna-gene-promoters
#19
Oleksandr Dergai, Pascal Cousin, Jerome Gouge, Karishma Satia, Viviane Praz, Tracy Kuhlman, Philippe Lhôte, Alessandro Vannini, Nouria Hernandez
RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i...
May 21, 2018: Genes & Development
https://www.readbyqxmd.com/read/29785877/hepatitis-b-virus-lymphotropism-emerging-details-and-challenges
#20
Shivali S Joshi, Carla S Coffin
The hepatitis B virus (HBV) is predominantly a hepatotropic virus but also infects cells of the lymphatic system. HBV genomes (DNA, messenger (m)RNA, covalently closed circular (ccc) DNA) and proteins have been found in extrahepatic sites such as peripheral blood mononuclear cells (PBMC), lymph nodes, spleen, bone marrow and cerebrospinal fluid. HBV entry into hepatocytes occurs by binding of the HBV preS1 surface protein to its specific receptor, the bile acid transporter, sodium taurocholate co-transporting polypeptide (NTCP)...
May 22, 2018: Biotechnology & Genetic Engineering Reviews
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