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Rna induced silencing complex

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https://www.readbyqxmd.com/read/29339208/targeted-shrna-loaded-liposome-complex-combined-with-focused-ultrasound-for-blood-brain-barrier-disruption-and-suppressing-glioma-growth
#1
Guanjian Zhao, Qin Huang, Feng Wang, Xiang Zhang, Jiangang Hu, Ying Tan, Ning Huang, Zhigang Wang, Zhibiao Wang, Yuan Cheng
Our previous studies have demonstrated that focused ultrasound (FUS) combined with DNA-loaded microbubbles (MBs) can induce noninvasive, reversible, local disruption of the blood brain barrier (BBB) and enable targeted exogenous gene transfer into the central nervous system. However, due to low gene loading or the absence of positive targeting, to date, there has been no therapeutic effect of MBs combined with FUS in tumor treatment. In the current study, we adopted a phospholipid complex that exhibited sufficient gene loading and peptide-mediated targeting to delay glioma growth...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29246303/site-specific-modification-using-the-2-methoxyethyl-group-improves-the-specificity-and-activity-of-sirnas
#2
Xinyun Song, Xiaoxia Wang, Yuan Ma, Zicai Liang, Zhenjun Yang, Huiqing Cao
Rapid progress has been made toward small interfering RNA (siRNA)-based therapy for human disorders, but rationally optimizing siRNAs for high specificity and potent silencing remains a challenge. In this study, we explored the effect of chemical modification at the cleavage site of siRNAs. We found that modifications at positions 9 and 10 markedly reduced the silencing potency of the unmodified strand of siRNAs but were well tolerated by the modified strand. Intriguingly, addition of the 2'-methoxyethyl (MOE) group at the cleavage site improved both the specificity and silencing activity of siRNAs by facilitating the oriented RNA-induced silencing complex (RISC) loading of the modified strand...
December 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29237752/ser7-of-rnapii-ctd-facilitates-heterochromatin-formation-by-linking-ncrna-to-rnai
#3
Takuya Kajitani, Hiroaki Kato, Yuji Chikashige, Chihiro Tsutsumi, Yasushi Hiraoka, Hiroshi Kimura, Yasuyuki Ohkawa, Chikashi Obuse, Damien Hermand, Yota Murakami
Some long noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (RNAPII) are retained on chromatin, where they regulate RNAi and chromatin structure. The molecular basis of this retention remains unknown. We show that in fission yeast serine 7 (Ser7) of the C-terminal domain (CTD) of RNAPII is required for efficient siRNA generation for RNAi-dependent heterochromatin formation. Surprisingly, Ser7 facilitates chromatin retention of nascent heterochromatic RNAs (hRNAs). Chromatin retention of hRNAs and siRNA generation requires both Ser7 and an RNA-binding activity of the chromodomain of Chp1, a subunit of the RNA-induced transcriptional silencing (RITS) complex...
December 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29236257/identifying-risc-components-using-ago2-immunoprecipitation-and-mass-spectrometry
#4
Tingfang Yi
Complex immunoprecipitation (Co-IP) is a powerful technique for precipitating an intact protein complex out of solution and cell lysates using an antibody that specifically binds to a particular protein in a large complex of proteins. Mass spectrometry (MS) is used to identify, sequence, and quantify proteins. RNA-induced silencing complexes (RISCs), Ago2 centered protein assemblies, are essential for miRNA mediated RNA decay and gene expression regulation; however, the complete list of RISCs is unknown. Here we describe methods used to combine IP and MS to identify new components of RISCs...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29229993/therapeutic-relevance-of-the-pp2a-b55-inhibitory-kinase-mastl-greatwall-in-breast-cancer
#5
Mónica Álvarez-Fernández, María Sanz-Flores, Belén Sanz-Castillo, María Salazar-Roa, David Partida, Elisabet Zapatero-Solana, H Raza Ali, Eusebio Manchado, Scott Lowe, Todd VanArsdale, David Shields, Carlos Caldas, Miguel Quintela-Fandino, Marcos Malumbres
PP2A is a major tumor suppressor whose inactivation is frequently found in a wide spectrum of human tumors. In particular, deletion or epigenetic silencing of genes encoding the B55 family of PP2A regulatory subunits is a common feature of breast cancer cells. A key player in the regulation of PP2A/B55 phosphatase complexes is the cell cycle kinase MASTL (also known as Greatwall). During cell division, inhibition of PP2A-B55 by MASTL is required to maintain the mitotic state, whereas inactivation of MASTL and PP2A reactivation is required for mitotic exit...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29222952/accumulation-of-the-coumarin-scopolin-under-abiotic-stress-conditions-is-mediated-by-the-arabidopsis-thaliana-tho-trex-complex
#6
Stefanie Döll, Markus Kuhlmann, Twan Rutten, Michael Florian Mette, Sarah Scharfenberg, Antonios Petridis, Dorothee-Carina Berreth, Hans-Peter Mock
Secondary metabolites are involved in plant stress response. Among these are scopolin and its active form scopoletin, which are coumarin-derivatives associated with reactive oxygen species scavenging and pathogen defence. Here we show that scopolin accumulation can be induced in the root by osmotic stress and in the leaf by low temperature stress in Arabidopsis thaliana. A genetic screen for altered scopolin levels in A. thaliana revealed a mutant compromised in scopolin accumulation in response to stress; the lesion was present in a homologue of THO1 coding for a subunit of the THO/TREX complex...
December 9, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29220657/hnrnpk-recruits-pcgf3-5-prc1-to-the-xist-rna-b-repeat-to-establish-polycomb-mediated-chromosomal-silencing
#7
Greta Pintacuda, Guifeng Wei, Chloë Roustan, Burcu Anil Kirmizitas, Nicolae Solcan, Andrea Cerase, Alfredo Castello, Shabaz Mohammed, Benoît Moindrot, Tatyana B Nesterova, Neil Brockdorff
The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119 ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However, the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a 600 nt sequence encompassing the Xist B-repeat element...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29211718/pirna-mediated-regulation-of-transposon-alternative-splicing-in-the-soma-and-germ-line
#8
Felipe Karam Teixeira, Martyna Okuniewska, Colin D Malone, Rémi-Xavier Coux, Donald C Rio, Ruth Lehmann
Transposable elements can drive genome evolution, but their enhanced activity is detrimental to the host and therefore must be tightly regulated. The Piwi-interacting small RNA (piRNA) pathway is vital for the regulation of transposable elements, by inducing transcriptional silencing or post-transcriptional decay of mRNAs. Here we show that piRNAs and piRNA biogenesis components regulate precursor mRNA splicing of P-transposable element transcripts in vivo, leading to the production of the non-transposase-encoding mature mRNA isoform in Drosophila germ cells...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29203416/quantitative-contributions-of-processes-by-which-polyanion-drugs-reduce-intracellular-bioavailability-and-transfection-efficiency-of-cationic-sirna-lipoplex
#9
Pharavee Jaiprasart, Bertrand Z Yeung, Ze Lu, M Guillaume Wientjes, Minjian Cui, Chien-Ming Hsieh, Sukyung Woo, Jessie L-S Au
RNA Interference (RNAi) is a potentially useful tool to correct the detrimental effects of faulty genes; several RNAi are undergoing clinical evaluation in various diseases. The present study identified the relative contributions of three mechanisms by which polyanion drugs reduced the gene silencing activity of Lipoplex, a complex of small interfering RNA (siRNA) and cationic liposomes. The study used a siRNA against the chemoresistance gene survivin and two model polyanion drugs (suramin, heparin). Products of Lipoplex destabilization were separated, identified, and/or quantified using ultrafiltration, gel electrophoresis, and RT-qPCR (quantitative reverse transcription polymerase chain reaction)...
December 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29201167/chaf1a-the-largest-subunit-of-the-chromatin-assembly-factor-1-complex-regulates-the-growth-of-h1299-human-non-small-cell-lung-cancer-cells-by-inducing-g0-g1-cell-cycle-arrest
#10
Tanzhen Liu, Jingjing Wei, Chao Jiang, Chen Wang, Xiaoqin Zhang, Yan Du, Jianqiang Li, Hui Zhao
Chromatin assembly factor 1 subunit A (CHAF1A) is the largest subunit of the chromatin assembly factor 1 (CAF-1) complex that is implicated in the assembly of nucleosomes on newly synthesized DNA. The aim of the present study was to determine its expression and biological function in non-small cell lung cancer (NSCLC). The current study examined the levels of CHAF1A expression in 22 samples of NSCLC and corresponding normal lung tissues. Subsequently, endogenous CHAF1A expression in H1299 NSCLC cells was knocked down via lentiviral delivery of CHAF1A-targeting short hairpin RNA (shRNA), and cell proliferation, colony formation and cell cycle distribution were measured...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29170131/negative-regulation-of-lncrna-gas5-by-mir-196a-inhibits-esophageal-squamous-cell-carcinoma-growth
#11
Kai Wang, Juan Li, Gang Xiong, Gang He, Xingying Guan, Kang Yang, Yun Bai
MiR-196a could play important roles in carcinogenesis by targeting many protein coding genes. However, little is known about whether miR-196a can target any long non-coding RNAs (lncRNAs). In the present study, we screen lncRNAs which are regulated by miRNA-196a in human esophageal squamous cell carcinoma (ESCC). We found that miR-196a could suppress the expression of lncRNA growth arrest-specific 5(GAS5). GAS5 is frequently down-regulated in 86 paired human ESCC tissues. Importantly, there was lower GAS5 expression in the late stage of ESCC patients...
November 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29164518/reducing-production-of-fumonisin-mycotoxins-in-fusarium-verticillioides-by-rna-interference
#12
Eric T Johnson, Robert H Proctor, Christopher A Dunlap, Mark Busman
The fungus Fusarium verticillioides is a maize pathogen that can produce fumonisin mycotoxins in ears under certain environmental conditions. Because fumonisins pose health risks to humans and livestock, control strategies with minimal risk to the environment are needed to reduce fumonisin contamination. Host-induced gene silencing is a promising technique in which double-stranded RNA expressed in the plant host is absorbed by an invading fungus and down-regulates genes critical for pathogenicity or mycotoxin production in the fungus...
November 22, 2017: Mycotoxin Research
https://www.readbyqxmd.com/read/29133395/rna-stem-structure-governs-coupling-of-dicing-and-gene-silencing-in-rna-interference
#13
Hye Ran Koh, Amirhossein Ghanbariniaki, Sua Myong
PremicroRNAs (premiRNAs) possess secondary structures consisting of a loop and a stem with multiple mismatches. Despite the well-characterized RNAi pathway, how the structural features of premiRNA contribute to dicing and subsequent gene-silencing efficiency remains unclear. Using single-molecule FISH, we demonstrate that cytoplasmic mRNA, but not nuclear mRNA, is reduced during RNAi. The dicing rate and silencing efficiency both increase in a correlated manner as a function of the loop length. In contrast, mismatches in the stem drastically diminish the silencing efficiency without impacting the dicing rate...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29132374/yeast-interfering-rna-larvicides-targeting-neural-genes-induce-high-rates-of-anopheles-larval-mortality
#14
Keshava Mysore, Limb K Hapairai, Longhua Sun, Elizabeth I Harper, Yingying Chen, Kathleen K Eggleson, Jacob S Realey, Nicholas D Scheel, David W Severson, Na Wei, Molly Duman-Scheel
BACKGROUND: Although larviciding can reduce the number of outdoor biting malaria vector mosquitoes, which may help to prevent residual malaria transmission, the current larvicide repertoire is faced with great challenges to sustainability. The identification of new effective, economical, and biorational larvicides could facilitate maintenance and expansion of the practice of larviciding in integrated malaria vector mosquito control programmes. Interfering RNA molecules represent a novel class of larvicides with untapped potential for sustainable mosquito control...
November 13, 2017: Malaria Journal
https://www.readbyqxmd.com/read/29115409/mechanism-of-long-non-coding-rna-malat1-in-lipopolysaccharide-induced-acute-kidney-injury-is-mediated-by-the-mir-146a-nf-%C3%AE%C2%BAb-signaling-pathway
#15
Ying Ding, Feng Guo, Tao Zhu, Jun Li, Danyan Gu, Weiliang Jiang, Yuying Lu, Daoyang Zhou
The present study aimed to examine the expression and function of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA (miR)-146a/nuclear factor (NF)-κB axis in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The mRNA levels of MALAT1 and miR-146a in AKI tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction analysis. The NF-κB pathway proteins and cell viability were assessed using western blot analysis and the MTT method, respectively...
November 2, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29075278/hop-sti1-a-two-faced-cochaperone-involved-in-pattern-recognition-receptor-maturation-and-viral-infection
#16
Christian E Lamm, Max E Kraner, Jörg Hofmann, Frederik Börnke, Hans-Peter Mock, Uwe Sonnewald
Perception of pathogens by host pattern recognition receptors (PRRs) or R proteins is a prerequisite to promote successful immune responses. The Hsp70/Hsp90 organizing protein Hop/Sti1, a multifunctional cochaperone, has been implicated in the maturation of a receptor-like kinase (RLK) necessary for chitin sensing. However, it remains unknown whether Hop/Sti1 is generally participating in PRR genesis. Using RNA-interference (RNAi), we silenced Hop/Sti1 expression in Nicotiana tabacum to gain further insight into the role of the cochaperone in plant defense responses...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29070679/the-e3-ubiquitin-ligase-scf-fbxl14-complex-stimulates-neuronal-differentiation-by-targeting-the-notch-signaling-factor-hes1-for-proteolysis
#17
Fangfang Chen, Chunxiao Zhang, Haonan Wu, Yue Ma, Xiaomin Luo, Xinqi Gong, Fan Jiang, Yaoting Gui, Hui Zhang, Fei Lu
Molecular oscillators are important cellular regulators of, for example, circadian clocks, oscillations of immune regulators, and short-period (ultradian) rhythms during embryonic development. The Notch signaling factor hairy and enhancer of split 1 (HES1) is a well-known repressor of proneural genes, and HES1 ultradian oscillation is essential for keeping cells in an efficiently proliferating progenitor state. HES1 oscillation is driven by both transcriptional self-repression and ubiquitin-dependent proteolysis...
October 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29070517/host-induced-gene-silencing-of-the-mapkk-gene-psfuz7-confers-stable-resistance-to-wheat-stripe-rust
#18
Xiaoguo Zhu, Tuo Qi, Qian Yang, Fuxin He, Chenglong Tan, Wei Ma, Ralf Thomas Voegele, Zhensheng Kang, Jun Guo
RNA interference (RNAi) is a powerful genetic tool to accelerate research in plant biotechnology and to control biotic stresses by manipulating target gene expression. However, the potential of RNAi in wheat to efficiently and durably control the devastating stripe rust fungus Puccinia striiformis f. sp. tritici (Pst), remained largely under explored, so far. To address this issue, we generated transgenic wheat lines expressing double-stranded RNA targeting PsFUZ7 transcripts of Pst. We analyzed expression of PsFUZ7 and related genes, and resistance traits of the transgenic wheat lines...
October 25, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29061908/the-rna-editing-factor-slorrm4-is-required-for-normal-fruit-ripening-in-tomato
#19
Yongfang Yang, Guoning Zhu, Rui Li, Shijie Yan, Daqi Fu, Benzhong Zhu, Huiqin Tian, Yunbo Luo, Hongliang Zhu
RNA editing plays a key posttranscriptional role in gene expression. Existing studies on cytidine-to-uridine RNA editing in plants have focused on maize (Zea mays), rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana). However, the importance and regulation of RNA editing in several critical agronomic processes are not well understood, a notable example of which is fruit ripening. Here, we analyzed the expression profile of 33 RNA editing factors and identified 11 putative tomato (Solanum lycopersicum) fruit ripening-related factors...
December 2017: Plant Physiology
https://www.readbyqxmd.com/read/29056324/the-dynamics-of-mrna-turnover-revealed-by-single-molecule-imaging-in-single-cells
#20
Ivana Horvathova, Franka Voigt, Anna V Kotrys, Yinxiu Zhan, Caroline G Artus-Revel, Jan Eglinger, Michael B Stadler, Luca Giorgetti, Jeffrey A Chao
RNA degradation plays a fundamental role in regulating gene expression. In order to characterize the spatiotemporal dynamics of RNA turnover in single cells, we developed a fluorescent biosensor based on dual-color, single-molecule RNA imaging that allows intact transcripts to be distinguished from stabilized degradation intermediates. Using this method, we measured mRNA decay in single cells and found that individual degradation events occur independently within the cytosol and are not enriched within processing bodies...
November 2, 2017: Molecular Cell
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