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https://www.readbyqxmd.com/read/29627294/%C3%AE-arrestin-biased-agonism-of-%C3%AE-adrenergic-receptor-regulates-dicer-mediated-microrna-maturation-to-promote-cardioprotective-signaling
#1
Jian-Peng Teoh, Ahmed S Bayoumi, Tatsuya Aonuma, Yanyan Xu, John A Johnson, Huabo Su, Neal L Weintraub, Yaoliang Tang, Il-Man Kim
RATIONALE: MicroRNAs (miRs) are small, non-coding RNAs that function to post-transcriptionally regulate target genes. First transcribed as primary miR transcripts (pri-miRs), they are enzymatically processed by Drosha into premature miRs (pre-miRs) and further cleaved by Dicer into mature miRs. Initially discovered to desensitize β-adrenergic receptor (βAR) signaling, β-arrestins are now well-appreciated to modulate multiple pathways independent of G protein signaling, a concept known as biased signaling...
April 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29626361/a-dicistronic-precursor-encoding-mir398-and-the-legume-specific-mir2119-co-regulates-csd1-and-adh1-mrnas-in-response-to-water-deficit
#2
Carlos De la Rosa, Alejandra Alicia Covarrubias, José Luis Reyes
Plant microRNAs are commonly encoded in transcripts containing a single microRNA precursor. Processing by DICER-LIKE 1 and associated factors results in the production of a small RNA, followed by its incorporation into an AGO-containing protein complex to guide silencing of an mRNA possessing a complementary target sequence. Certain microRNA loci contain more that one precursor stem-loop structure, thus encoding more than one microRNA in the same transcript. Here we describe a unique case where the evolutionary-conserved miR398a is encoded in the same transcript as the legume-specific miR2119...
April 6, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29602831/bioengineered-ncrnas-selectively-change-cellular-mirnome-profiles-for-cancer-therapy
#3
Pui Yan Ho, Zhijian Duan, Neelu Batra, Joseph L Jilek, Mei-Juan Tu, Jing-Xin Qiu, Zihua Hu, Theodore Wun, Primo N Lara, Ralph W DeVere White, Hong-Wu Chen, Ai-Ming Yu
Noncoding RNAs (ncRNAs) produced in live cells may better reflect intracellular ncRNAs for research and therapy. Attempts were made to produce biological ncRNAs, but at low yield or success rate. Here we first report a new ncRNA bioengineering technology, using more stable ncRNA carrier (nCAR) containing a pre-miR-34a derivative identified by rational design and experimental validation. This approach offered a remarkable higher-level expression (40-80% of total RNAs) of recombinant ncRNAs in bacteria, and gave an 80% success rate (33 out of 42 ncRNAs)...
March 30, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29601972/complexation-of-chol-dsirna-in-place-of-chol-sirna-greatly-increases-the-duration-of-mrna-suppression-by-polyplexes-of-pll-30-peg-5k-in-primary-murine-syngeneic-breast-tumors-after-i-v-administration
#4
Vishakha V Ambardekar, Rajesh R Wakaskar, Zhen Ye, Stephen M Curran, Timothy R McGuire, Don W Coulter, Rakesh K Singh, Joseph A Vetro
RNA interference has tremendous potential for cancer therapy but is limited by the insufficient potency of RNAi molecules after i.v. administration. We previously found that complexation with PLL(30)-PEG(5K) greatly increases the potency of 3'-cholesterol-modified siRNA [Chol-siRNA] in primary murine syngeneic 4T1 breast tumors after i.v. administration but mRNA suppression decreases 24 hours after the final dose. We hypothesized that complexation of cholesterol-modified Dicer-substrate siRNA (Chol-DsiRNA) in place of Chol-siRNA can increase the potency and duration of suppression by polyplexes of PLL(30)-PEG(5K) in solid tumors...
March 27, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29601523/genome-wide-analysis-of-dcl-ago-and-rdr-gene-families-in-pepper-capsicum-annuum-l
#5
Lei Qin, Ning Mo, Tayeb Muhammad, Yan Liang
RNA silencing is an evolutionarily conserved mechanism that regulates variety of cellular processes in plants. Argonaute protein (AGO), Dicer-like protein (DCL) and RNA-dependent RNA polymerase (RDR) are critical components of RNA silencing. These efficient and indispensable components of the RNAi pathway have not been identified and characterized in pepper. In this study, we identified 12 CaAGO , 4 CaDCL and 6 CaRDR genes in pepper and compared them with those of Arabidopsis, tobacco, potato and tomato. Detailed phylogenetic analyses revealed that each CaAGO, CaDCL and CaRDR protein family were classified into four clades...
March 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29600985/role-of-components-of-microrna-machinery-in-carcinogenesis
#6
R Kian, S Moradi, S Ghorbian
MicroRNAs (miRNAs) are a broad class of non-coding RNAs nearly 21 nucleotides length, which play crucial functions in post-transcriptional gene regulation. These molecules are associated with many developmental and cellular processes in eukaryotic organisms. Current investigation has reported major factors contributing to miRNA biogenesis and has constituted basic principles of miRNA function. More recently, it was confirmed that various miRNAs are clearly implicated in human malignancies, such as lung, breast, ovarian, bladder, colon cancer and other kinds of carcinoma...
March 2018: Experimental Oncology
https://www.readbyqxmd.com/read/29570195/dna-nanoclew-templated-spherical-nucleic-acids-for-sirna-delivery
#7
Weimin Ruan, Meng Zheng, Yang An, Yuanyuan Liu, David B Lovejoy, Mingcong Hao, Yan Zou, Albert Lee, Shu Yang, Yiqing Lu, Marco Morsch, Roger Chung, Bingyang Shi
A superior biocompatible spherical nucleic acid (SNA) conjugate was fabricated by grafting siRNA onto the surface of a core composed of a spherical DNA nanostructure that we have termed a DNA nanoclew (DC). After uptake by cultured cancer cells, SNA nanoparticles release engrafted siRNAs by cleavage of the intracellular Dicer enzyme. Moreover, in vitro experiments reveal that such SNAs demonstrate potent gene knockdown at both mRNA and protein levels, while with negligible cytotoxicity.
March 23, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29563539/an-nf90-nf110-mediated-feedback-amplification-loop-regulates-dicer-expression-and-controls-ovarian-carcinoma-progression
#8
Jérôme Barbier, Xin Chen, Gabriel Sanchez, Muyan Cai, Marion Helsmoortel, Takuma Higuchi, Pierre Giraud, Xavier Contreras, Gangjun Yuan, Zihao Feng, Rima Nait-Saidi, Olivier Deas, Lisa Bluy, Jean-Gabriel Judde, Sylvie Rouquier, William Ritchie, Shuji Sakamoto, Dan Xie, Rosemary Kiernan
Reduced expression of DICER, a key enzyme in the miRNA pathway, is frequently associated with aggressive, invasive disease, and poor survival in various malignancies. Regulation of DICER expression is, however, poorly understood. Here, we show that NF90/NF110 facilitates DICER expression by controlling the processing of a miRNA, miR-3173, which is embedded in DICER pre-mRNA. As miR-3173 in turn targets NF90, a feedback amplification loop controlling DICER expression is established. In a nude mouse model, NF90 overexpression reduced proliferation of ovarian cancer cells and significantly reduced tumor size and metastasis, whereas overexpression of miR-3173 dramatically increased metastasis in an NF90- and DICER-dependent manner...
March 21, 2018: Cell Research
https://www.readbyqxmd.com/read/29563500/nc886-is-induced-by-tgf-%C3%AE-and-suppresses-the-microrna-pathway-in-ovarian-cancer
#9
Ji-Hye Ahn, Hyun-Sung Lee, Ju-Seog Lee, Yeon-Su Lee, Jong-Lyul Park, Seon-Young Kim, Jung-Ah Hwang, Nawapol Kunkeaw, Sung Yun Jung, Tae Jin Kim, Kwang-Soo Lee, Sung Ho Jeon, Inhan Lee, Betty H Johnson, Jung-Hye Choi, Yong Sun Lee
Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies...
March 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29562912/gas5-is-an-essential-lncrna-regulator-for-self-renewal-and-pluripotency-of-mouse-embryonic-stem-cells-and-induced-pluripotent-stem-cells
#10
Jiajie Tu, Geng Tian, Hoi-Hung Cheung, Wei Wei, Tin-Lap Lee
BACKGROUND: The regulatory role of long noncoding RNAs (lncRNAs) have been partially proved in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). METHODS: In the current study, we investigated mouse ESC (mESC) self-renewal, differentiation, and proliferation in vitro by knocking down a lncRNA, growth arrest specific 5 (Gas5). A series of related indicators were examined by cell counting kit-8 (CCK-8) assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, alkaline phosphatase staining, propidium iodide (PI) staining, Annexin V staining, competition growth assay, immunofluorescence, and chromatin immunoprecipitation (ChIP)-qPCR...
March 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29556342/receptor-targeted-aptamer-sirna-conjugate-directed-transcriptional-regulation-of-hiv-1
#11
Jiehua Zhou, Daniel Lazar, Haitang Li, Xin Xia, Sangeetha Satheesan, Paige Charlins, Denis O'Mealy, Ramesh Akkina, Sheena Saayman, Marc S Weinberg, John J Rossi, Kevin V Morris
Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR)...
2018: Theranostics
https://www.readbyqxmd.com/read/29552298/synergistic-neuroprotective-effect-of-rasagiline-and-idebenone-against-retinal-ischemia-reperfusion-injury-via-the-lin28-let-7-dicer-pathway
#12
Dawei Lei, Zhengbo Shao, Xinrong Zhou, Huiping Yuan
Retinal ischemia-reperfusion (RIR) injury causes neuronal degeneration and initiates various optic nerve diseases. This study aimed to investigate the synergistic neuroprotective effect of rasagiline and idebenone against RIR injury. A combination of rasagiline and idebenone was administered intraperitoneally immediately after establishment of the RIR model. Treatment with the combination of the two drugs resulted in a significant restoration of retinal thickness and retinal ganglion cells. Apoptosis of cells in ganglion cell layers was also ameliorated, suggesting that the effect of the two drugs was synergistic and the expression of brain-derived neurotrophic factor increased...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29551264/dicer-like-enzymes-with-sequence-cleavage-preferences
#13
Cristina Hoehener, Iris Hug, Mariusz Nowacki
Dicer proteins are known to produce small RNAs (sRNAs) from long double-stranded RNA (dsRNA) templates. These sRNAs are bound by Argonaute proteins, which select the guide strand, often with a 5' end sequence bias. However, Dicer proteins have never been shown to have sequence cleavage preferences. In Paramecium development, two classes of sRNAs that are required for DNA elimination are produced by three Dicer-like enzymes: Dcl2, Dcl3, and Dcl5. Through in vitro cleavage assays, we demonstrate that Dcl2 has a strict size preference for 25 nt and a sequence preference for 5' U and 5' AGA, while Dcl3 has a sequence preference for 5' UNG...
March 1, 2018: Cell
https://www.readbyqxmd.com/read/29550490/loquacious-pd-removes-phosphate-inhibition-of-dicer-2-processing-of-hairpin-rnas-into-sirnas
#14
Ryuya Fukunaga
Drosophila Dicer-2 processes RNA substrates into short interfering RNAs (siRNAs). Loquacious-PD (Loqs-PD), a dsRNA-binding protein that associates with Dicer-2, is required for processing of a subset of RNA substrates including hairpin RNAs into siRNAs. Inorganic phosphate-a small molecule present in all cell types-inhibits Dicer-2 from processing precursor of microRNAs (pre-miRNAs), which are processed by Dicer-1. Whether or how Loqs-PD modulates the inhibitory effect of inorganic phosphate on Dicer-2 processing of RNA substrates is unknown...
March 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29545204/baculovirus-driven-protein-expression-in-insect-cells-a-benchmarking-study
#15
Peggy Stolt-Bergner, Christian Benda, Tim Bergbrede, Hüseyin Besir, Patrick H N Celie, Cindy Chang, David Drechsel, Ariane Fischer, Arie Geerlof, Barbara Giabbai, Joop van den Heuvel, Georg Huber, Wolfgang Knecht, Anita Lehner, Regis Lemaitre, Kristina Nordén, Gwynn Pardee, Ines Racke, Kim Remans, Astrid Sander, Judith Scholz, Magda Stadnik, Paola Storici, Daniel Weinbruch, Isabel Zaror, Linda H L Lua, Sabine Suppmann
Baculovirus-insect cell expression system has become one of the most widely used eukaryotic expression systems for heterologous protein production in many laboratories. The availability of robust insect cell lines, serum-free media, a range of vectors and commercially-packaged kits have supported the demand for maximizing the exploitation of the baculovirus-insect cell expression system. Naturally, this resulted in varied strategies adopted by different laboratories to optimize protein production. Most laboratories have preference in using either the E...
March 12, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29540675/expression-of-lncrna-mir222hg-co-transcribed-from-the-mir-221-222-gene-promoter-facilitates-the-development-of-castration-resistant-prostate-cancer
#16
Tong Sun, Shin-Yi Du, Joshua Armenia, Fangfang Qu, Jingyu Fan, Xiaodong Wang, Teng Fei, Kazumasa Komura, Shirley X Liu, Gwo-Shu Mary Lee, Philip W Kantoff
Mechanisms by which non-coding RNAs contribute to the progression of hormone-sensitive prostate cancer (PCa) (HSPC) to castration-resistant PCa (CRPC) remain largely unknown. We previously showed that microRNA-221/222 is up-regulated in CRPC and plays a critical role in modulating androgen receptor function during CRPC development. With further investigation, we characterized a putative promoter region located 23.3 kb upstream of the miR-221/222 gene, and this promoter is differentially activated in CRPC LNCaP-Abl cells, leading to the up-regulation of miR-221/222...
March 13, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29522510/coordinated-regulation-of-arabidopsis-microrna-biogenesis-and-red-light-signaling-through-dicer-like-1-and-phytochrome-interacting-factor-4
#17
Zhenfei Sun, Min Li, Ying Zhou, Tongtong Guo, Yin Liu, Hui Zhang, Yuda Fang
Light and microRNAs (miRNAs) are key external and internal signals for plant development, respectively. However, the relationship between the light signaling and miRNA biogenesis pathways remains unknown. Here we found that miRNA processer proteins DCL1 and HYL1 interact with a basic helix-loop-helix (bHLH) transcription factor, phytochrome-interacting factor 4 (PIF4), which mediates the destabilization of DCL1 during dark-to-red-light transition. PIF4 acts as a transcription factor for some miRNA genes and is necessary for the proper accumulation of miRNAs...
March 9, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29521232/role-of-mir-193a-in-cancer-complexity-and-factors-control-the-pattern-of-its-expression
#18
Afraa Mamoori, Vinod Gopalan, Alfred K-Y Lam
BACKGROUND: There is emerging data suggest that the non-coding RNA (microRNA 193a or miR-193a) plays key roles in different types of cancers. OBJECTIVE: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature. METHOD: All the literature concerning miR-193a in cancer in PubMed are analysed. RESULTS: Several studies proved the association of miR-193a expression patterns with cancer's stages, grades, response to the chemotherapy and even patient survival...
March 7, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29504892/comparing-mirna-structure-of-mirtrons-and-non-mirtrons
#19
Igor I Titov, Pavel S Vorozheykin
BACKGROUND: MicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA. RESULTS: We found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer...
February 9, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29503180/dicer-2-dependent-generation-of-viral-dna-from-defective-genomes-of-rna-viruses-modulates-antiviral-immunity-in-insects
#20
Enzo Z Poirier, Bertsy Goic, Lorena Tomé-Poderti, Lionel Frangeul, Jérémy Boussier, Valérie Gausson, Hervé Blanc, Thomas Vallet, Hyelee Loyd, Laura I Levi, Sophie Lanciano, Chloé Baron, Sarah H Merkling, Louis Lambrechts, Marie Mirouze, Susan Carpenter, Marco Vignuzzi, Maria-Carla Saleh
The RNAi pathway confers antiviral immunity in insects. Virus-specific siRNA responses are amplified via the reverse transcription of viral RNA to viral DNA (vDNA). The nature, biogenesis, and regulation of vDNA are unclear. We find that vDNA produced during RNA virus infection of Drosophila and mosquitoes is present in both linear and circular forms. Circular vDNA (cvDNA) is sufficient to produce siRNAs that confer partially protective immunity when challenged with a cognate virus. cvDNAs bear homology to defective viral genomes (DVGs), and DVGs serve as templates for vDNA and cvDNA synthesis...
February 27, 2018: Cell Host & Microbe
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