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RNA binding proteins

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https://www.readbyqxmd.com/read/28938588/calreticulin-modulates-the-intracellular-survival-of-mycobacteria-by-regulating-er-stress-mediated-apoptosis
#1
Sung Hee Jo, Ji-Ae Choi, Yun-Ji Lim, Junghwan Lee, Soo-Na Cho, Sung-Man Oh, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938586/the-long-noncoding-rna-hotair-activates-the-hippo-pathway-by-directly-binding-to-sav1-in-renal-cell-carcinoma
#2
Guanghui Hu, Binbin Dong, Jingwei Zhang, Wei Zhai, Tiancheng Xie, Bisheng Huang, Chi Huang, Xudong Yao, Junhua Zheng, Jianping Che, Yun-Fei Xu
The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937734/discovery-of-oligonucleotide-signaling-mediated-by-crispr-associated-polymerases-solves-two-puzzles-but-leaves-an-enigma
#3
Eugene V Koonin, Kira S Makarova
The signature component of type III CRISPR-Cas systems is the Cas10 protein that consists of two Palm domains homologous to those of DNA and RNA polymerases, and nucleotide cyclases, and an HD nuclease domain. However, until very recently, the activity of the Palm domains and their role in CRISPR function have not been experimentally established. Most of the type III CRISPR-Cas systems and some type I systems also encompass proteins containing the CARF (CRISPR-associated Rossmann fold) domain that has been predicted to regulate CRISPR functions via nucleotide binding but its function in CRISPR-Cas remained obscure...
September 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28937658/extracellular-vesicle-associated-rna-as-a-carrier-of-epigenetic-information
#4
REVIEW
Carlo Maria Di Liegro, Gabriella Schiera, Italia Di Liegro
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5'- and 3'-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes...
September 22, 2017: Genes
https://www.readbyqxmd.com/read/28935965/aromatic-side-chain-conformational-switch-on-the-surface-of-the-rna-recognition-motif-enables-rna-discrimination
#5
Nana Diarra Dit Konté, Miroslav Krepl, Fred F Damberger, Nina Ripin, Olivier Duss, Jiří Šponer, Frédéric H-T Allain
The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5'-UUUAA-3' originating from the COX-2 3'-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high- or low-affinity binding with functional implications...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935901/a-brain-targeting-lipidated-peptide-for-neutralizing-rna-mediated-toxicity-in-polyglutamine-diseases
#6
Qian Zhang, Mengbi Yang, Kasper K Sørensen, Charlotte S Madsen, Josephine T Boesen, Ying An, Shao Hong Peng, Yuming Wei, Qianwen Wang, Knud J Jensen, Zhong Zuo, Ho Yin Edwin Chan, Jacky Chi Ki Ngo
Polyglutamine (PolyQ) diseases are progressive neurodegenerative disorders caused by both protein- and RNA-mediated toxicities. We previously showed that a peptidyl inhibitor, P3, which binds directly to expanded CAG RNA can inhibit RNA-induced nucleolar stress and suppress RNA-induced neurotoxicity. Here we report a N-acetylated and C-amidated derivative of P3, P3V8, that showed a more than 20-fold increase in its affinity for expanded CAG RNA. The P3V8 peptide also more potently alleviated expanded RNA-induced cytotoxicity in vitro, and suppressed polyQ neurodegeneration in Drosophila with no observed toxic effects...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935721/the-spliceosomal-proteins-ppih-and-prpf4-exhibit-bipartite-binding
#7
Caroline Rajiv, S RaElle Jackson, Simon Cocklin, Elan Z Eisenmesser, Tara Davis
Pre-mRNA splicing is a dynamic, multi-step process that is catalyzed by the RNA: protein complex called the spliceosome. The spliceosome contains a core set of RNAs and proteins that are conserved in all organisms that perform splicing. In higher organisms, PPIH directly interacts with the core protein PRPF4 and both integrate into the pre-catalytic spliceosome as part of the tri-snRNP sub-complex. As a first step to understand the protein interactions that dictate PPIH and PRPF4 function, we expressed and purified soluble forms of each protein and formed a complex between them...
September 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28935708/unraveling-transcriptome-dynamics-in-human-spermatogenesis
#8
S Z Jan, T L Vormer, A Jongejan, M Röling, S J Silber, D G de Rooij, G Hamer, S Repping, A M M van Pelt
Spermatogenesis is a dynamic developmental process that includes stem cell proliferation and differentiation, meiotic cell divisions and extreme chromatin condensation. Although studied in mice, the molecular control of human spermatogenesis is largely unknown. Here, we developed a protocol that enables next generation sequencing of RNA obtained from pools of 500 individually laser capture microdissected cells of specific germ cell-subtypes from fixed human testis samples. Transcriptomic analyses of these successive germ cell subtypes reveals dynamic transcription of over 4000 genes during human spermatogenesis...
September 21, 2017: Development
https://www.readbyqxmd.com/read/28935369/a-three-dimensional-model-of-rnase-p-in-the-hyperthermophilic-archaeon-pyrococcus-horikoshii-ot3
#9
Xuzhu Gao, Kosuke Oshima, Toshifumi Ueda, Takashi Nakashima, Makoto Kimura
Ribonuclease P (RNase P) is an endoribonuclease involved in maturation of the 5'-end of tRNA. We found previously that RNase P in the hyperthermophilic archaeon Pyrococcus horikoshii OT3 consists of a catalytic RNase P RNA (PhopRNA) and five protein cofactors designated PhoPop5, PhoRpp21, PhoRpp29, PhoRpp30, and PhoRpp38. The crystal structures of the five proteins have been determined, a three-dimensional (3-D) model of PhopRNA has been constructed, and biochemical data, including protein-RNA interaction sites, have become available...
September 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28934490/number-of-inadvertent-rna-targets-for-morpholino-knockdown-in-danio-rerio-is-largely-underestimated-evidence-from-the-study-of-ser-arg-rich-splicing-factors
#10
Marine Joris, Marie Schloesser, Denis Baurain, Marc Hanikenne, Marc Muller, Patrick Motte
Although the involvement of Ser/Arg-rich (SR) proteins in RNA metabolism is well documented, their role in vertebrate development remains elusive. We, therefore, elected to take advantage of the zebrafish model organism to study the SR genes' functions using the splicing morpholino (sMO) microinjection and the programmable site-specific nucleases. Consistent with previous research, we revealed discrepancies between the mutant and morphant phenotypes and we show that these inconsistencies may result from a large number of unsuspected inadvertent morpholino RNA targets...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934484/regulation-of-hur-structure-and-function-by-dihydrotanshinone-i
#11
Preet Lal, Linda Cerofolini, Vito Giuseppe D'Agostino, Chiara Zucal, Carmelo Fuccio, Isabelle Bonomo, Erik Dassi, Stefano Giuntini, Danilo Di Maio, Vikalp Vishwakarma, Ranjan Preet, Sha Neisha Williams, Max S Fairlamb, Rachel Munk, Elin Lehrmann, Kotb Abdelmohsen, Saioa R Elezgarai, Claudio Luchinat, Ettore Novellino, Alessandro Quattrone, Emiliano Biasini, Leonardo Manzoni, Myriam Gorospe, Dan A Dixon, Pierfausto Seneci, Luciana Marinelli, Marco Fragai, Alessandro Provenzani
The Human antigen R protein (HuR) is an RNA-binding protein that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, and post-transcriptionally regulates the fate of target RNAs. The natural product dihydrotanshinone-I (DHTS) prevents the association of HuR and target RNAs in vitro and in cultured cells by interfering with the binding of HuR to RNA. Here, we report the structural determinants of the interaction between DHTS and HuR and the impact of DHTS on HuR binding to target mRNAs transcriptome-wide...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934469/hnrnp-l-controls-hpv16-rna-polyadenylation-and-splicing-in-an-akt-kinase-dependent-manner
#12
Naoko Kajitani, Jacob Glahder, Chengjun Wu, Haoran Yu, Kersti Nilsson, Stefan Schwartz
Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified 'hot spots' for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#13
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28934222/endogenous-rgs14-is-a-cytoplasmic-nuclear-shuttling-protein-that-localizes-to-juxtanuclear-membranes-and-chromatin-rich-regions-of-the-nucleus
#14
Mary Rose Branch, John R Hepler
Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and H-Ras/MAPkinase signaling pathways to regulate synaptic plasticity important for hippocampal learning and memory. However, to date, little is known about the subcellular distribution and roles of endogenous RGS14 in a neuronal cell line. Most of what is known about RGS14 cellular behavior is based on studies of tagged, recombinant RGS14 ectopically overexpressed in unnatural host cells. Here, we report for the first time a comprehensive assessment of the subcellular distribution and dynamic localization of endogenous RGS14 in rat B35 neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28934090/adipogenic-effects-and-gene-expression-profiling-of-firemaster%C3%A2-550-components-in-human-primary-preadipocytes
#15
Emily W Y Tung, Vian Peshdary, Remi Gagné, Andrea Rowan-Carroll, Carole L Yauk, Adéle Boudreau, Ella Atlas
BACKGROUND: Exposure to flame retardants has been associated with negative health outcomes including metabolic effects. As polybrominated diphenyl ether flame retardants were pulled from commerce, human exposure to new flame retardants such as Firemaster® 550 (FM550) has increased. Although previous studies in murine systems have shown that FM550 and its main components increase adipogenesis, the effects of FM550 in human models have not been elucidated. OBJECTIVES: The objectives of this study were to determine if FM550 and its components are active in human preadipocytes, and to further investigate their mode of action...
September 14, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28934014/nucleoplasmic-nup98-controls-gene-expression-by-regulating-a-dexh-d-box-protein
#16
Juliana S Capitanio, Ben Montpetit, Richard W Wozniak
The nucleoporin Nup98 has been linked to the regulation of transcription and RNA metabolism, (1-3) but the mechanisms by which Nup98 contributes to these processes remains largely undefined. Recently, we uncovered interactions between Nup98 and several DExH/D-box proteins (DBPs), a protein family well-known for modulating gene expression and RNA metabolism. (4-6) Analysis of Nup98 and one of these DBPs, DHX9, showed that they directly interact, their association is facilitated by RNA, and Nup98 binding stimulates DHX9 ATPase activity...
September 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28931862/long-non-coding-rna-hotair-promotes-cell-migration-by-upregulating-insulin-growth-factor-binding-protein-2-in-renal-cell-carcinoma
#17
Hiromichi Katayama, Keiichi Tamai, Rie Shibuya, Mao Nakamura, Mai Mochizuki, Kazunori Yamaguchi, Sadafumi Kawamura, Tatsuo Tochigi, Ikuro Sato, Takamasa Okanishi, Kunie Sakurai, Wataru Fujibuchi, Yoichi Arai, Kennichi Satoh
Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931603/the-pyhin-protein-p205-regulates-the-inflammasome-by-controlling-asc-expression
#18
Sreya Ghosh, Christina Wallerath, Sergio Covarrubias, Veit Hornung, Susan Carpenter, Katherine A Fitzgerald
Members of the IFN-inducible PYHIN protein family, such as absent in melanoma-2 and IFN-γ-inducible protein (IFI)16, bind dsDNA and form caspase-1-activating inflammasomes that are important in immunity to cytosolic bacteria, DNA viruses, or HIV. IFI16 has also been shown to regulate transcription of type I IFNs during HSV infection. The role of other members of the PYHIN protein family in the regulation of immune responses is much less clear. In this study, we identified an immune-regulatory function for a member of the murine PYHIN protein family, p205 (also called Ifi205)...
September 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28931413/topological-organization-and-dynamic-regulation-of-human-trna-genes-during-macrophage-differentiation
#19
Kevin Van Bortle, Douglas H Phanstiel, Michael P Snyder
BACKGROUND: The human genome is hierarchically organized into local and long-range structures that help shape cell-type-specific transcription patterns. Transfer RNA (tRNA) genes (tDNAs), which are transcribed by RNA polymerase III (RNAPIII) and encode RNA molecules responsible for translation, are dispersed throughout the genome and, in many cases, linearly organized into genomic clusters with other tDNAs. Whether the location and three-dimensional organization of tDNAs contribute to the activity of these genes has remained difficult to address, due in part to unique challenges related to tRNA sequencing...
September 20, 2017: Genome Biology
https://www.readbyqxmd.com/read/28931210/long-noncoding-rna-pcat-1-promotes-invasion-and-metastasis-via-the-mir-129-5p-hmgb1-signaling-pathway-in-hepatocellular-carcinoma
#20
Deyuan Zhang, Jinyu Cao, Qingling Zhong, Liangtao Zeng, Chang Cai, Lang Lei, Wen Zhang, Fanrong Liu
OBJECTIVE: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 1(PCAT-1) has been shown to be dysregulated and exert vital roles in tumorigenesis and progression of various malignancies. However, the precise molecular mechanism in the metastasis and invasion of HCC remain unclear. METHODS: The expression levels of PCAT1 derived from human HCC tissues and cell lines were analyzed through quantitative real-time PCR. QRT-PCR was also applied to detect the expression of HMGB1 and miR-129-5p...
September 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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