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https://www.readbyqxmd.com/read/29468672/ca-v-3-2-drives-sustained-burst-firing-which-is-critical-for-absence-seizure-propagation-in-reticular-thalamic-neurons
#1
Stuart M Cain, John R Tyson, Hyun-Beom Choi, Rebecca Ko, Paulo J C Lin, Jeffrey M LeDue, Kim L Powell, Louis-Philippe Bernier, Ravi L Rungta, Yi Yang, Pieter R Cullis, Terence J O'Brien, Brian A MacVicar, Terrance P Snutch
OBJECTIVE: Genetic alterations have been identified in the CACNA1H gene, encoding the CaV 3.2 T-type calcium channel in patients with absence epilepsy, yet the precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD) pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN) express high levels of CaV 3.2 calcium channels, and we investigated whether a gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the TRN...
February 21, 2018: Epilepsia
https://www.readbyqxmd.com/read/29467169/functional-redundancy-of-dicer-co-factors-tarbp2-and-prkra-during-murine-embryogenesis-does-not-involve-mirna-biogenesis
#2
Sri Ramulu N Pullagura, Bill Buaas, Nichelle Gray, Lindsey C Krening, Anuj Srivastava, Robert E Braun
Several in vitro studies suggest canonical miRNA biogenesis requires the DICER co-factors TARBP2 and PRKRA for processing of pre-miRNAs to mature miRNAs. To investigate the roles of TARBP2 and PRKRA in miRNA biogenesis in vivo , and to determine possible functional redundancy, we first compared the phenotypes of Tarbp2 and Prkra single and double-mutants. In contrast to Dicer-/- embryos, which die by E7.5, single Tarbp2-/- and Prkra-/- mice survive beyond E7.5 and either die peri-natally, or survive and exhibit cranial/facial abnormalities, respectively...
February 21, 2018: Genetics
https://www.readbyqxmd.com/read/29459484/when-trbp-leaves-dicer-at-the-alt-er
#3
Eran Hornstein
No abstract text is available yet for this article.
February 19, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29456377/molecular-simulation-studies-of-3-3-diindolylmethane-as-a-potent-microrna-21-antagonist
#4
Md Junaid, Raju Dash, Nazrul Islam, Jui Chowdhury, Md Jahangir Alam, Saikat Dev Nath, Mohammad Abu Sayem Shakil, Ashifa Azam, Syed Mustyen Quader, S M Zahid Hosen
Objective: In recent decades, the overexpression of microRNA-21 (miR-21) is found to be progressively linked with many diseases such as different types of cancers, cardiovascular diseases, and inflammation. Thereby, it has become an attractive target for pharmacological and genetic modulation in various diseases, and also for overcoming the resistance to chemotherapy in several cancers. Here, in this study, the role of molecular therapeutics of 3,3'-diindolylmethane (DIM) has been investigated for its ability to bind with the precursor miRNA as a target of miR-21 (hsa-mir-21), which may alter the catalyzation process of dicer, a RNase III enzyme, involved in miRNA transcription...
October 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/29453851/dicer-inactivation-stimulates-limb-regeneration-ability-in-xenopus-laevis
#5
Mengshi Zhang, Li Yang, Feng Yuan, Ying Chen, Gufa Lin
The ontogenetic decline of regeneration capacity in the anuran amphibian Xenopus makes it an excellent model for regeneration studies. However, the cause of the regeneration ability decline is not fully understood. MicroRNAs regulate animal development, and have been indicated in various regeneration situations. However, little is known about the role of microRNAs during limb regeneration in Xenopus. This study investigates the effect of Dicer, an enzyme responsible for microRNA maturation, on limb development and regeneration in Xenopus...
February 17, 2018: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29449323/structural-basis-of-sirna-recognition-by-trbp-double-stranded-rna-binding-domains
#6
Gregoire Masliah, Christophe Maris, Sebastian Lb König, Maxim Yulikov, Florian Aeschimann, Anna L Malinowska, Julie Mabille, Jan Weiler, Andrea Holla, Juerg Hunziker, Nicole Meisner-Kober, Benjamin Schuler, Gunnar Jeschke, Frederic H-T Allain
The accurate cleavage of pre-micro(mi)RNAs by Dicer and mi/siRNA guide strand selection are important steps in forming the RNA-induced silencing complex (RISC). The role of Dicer binding partner TRBP in these processes remains poorly understood. Here, we solved the solution structure of the two N-terminal dsRNA binding domains (dsRBDs) of TRBP in complex with a functionally asymmetric siRNA using NMR, EPR, and single-molecule spectroscopy. We find that siRNA recognition by the dsRBDs is not sequence-specific but rather depends on the RNA shape...
February 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29445371/effects-of-microrna-on-regulatory-t-cells-and-implications-for-adoptive-cellular-therapy-to-ameliorate-graft-versus-host-disease
#7
REVIEW
Keli L Hippen, Michael Loschi, Jemma Nicholls, Kelli P A MacDonald, Bruce R Blazar
Regulatory T cells (Tregs) are key mediators of the immune system. MicroRNAs (miRNAs) are a family of ~22 nucleotide non-coding RNAs that are processed from longer precursors by the RNases Drosha and Dicer. miRNA regulates protein expression posttranscriptionally through mRNA destabilization or translational silencing. A critical role for miRNA in Treg function was initially discovered when both Dicer and Drosha knockout (KO) mice were found to develop a fatal autoimmune disease phenotypically similar to Foxp3 KO mice...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29439213/a-genetic-network-for-systemic-rna-silencing-in-plants
#8
Wei Wei Chen, Xian Zhang, Yaya Fan, Bin Li, Eugene Ryabov, Nongnong Shi, Mei Zhao, Zhiming Yu, Cheng Qin, Qianqian Zheng, Pengcheng Zhang, Huizhong Wang, Stephen Jackson, Qi Cheng, Yule Liu, Philippe Gallusci, Yiguo Hong
Non-cell autonomous RNA silencing can spread from cell to cell and over long-distance in animals and plants. However, the genetic requirements and signals involved in plant mobile silencing remain poorly understood. Here, we identified a DICER-LIKE2 (DCL2)-dependent mechanism for systemic spread of post-transcriptional RNA silencing (also known as post-transcriptional gene silencing, PTGS) in Nicotiana benthamiana. Using a suite of transgenic DCL RNAi lines coupled with a GFP reporter, we demonstrated that N...
February 8, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29435920/target-mrna-driven-biogenesis-of-cognate-micrornas-in-vitro
#9
Mainak Bose, Suvendra N Bhattacharyya
miRNAs are 20-22 nucleotide long noncoding RNAs that act as post-transcriptional regulators of gene expression controlling more than half of protein coding genes in humans. Being the critical modulators of the mRNA translation process, biogenesis, function, and turnover of these small RNAs are tightly regulated in cells. We have reported that target mRNAs induce increased biogenesis of cognate miRNAs from pre-miRNAs by increased activity of Ago-associated Dicer endonuclease that processes precursor miRNAs to their mature form...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29432414/eat1-transcription-factor-a-non-cell-autonomous-regulator-of-pollen-production-activates-meiotic-small-rna-biogenesis-in-rice-anther-tapetum
#10
Seijiro Ono, Hua Liu, Katsutoshi Tsuda, Eigo Fukai, Keisuke Tanaka, Takuji Sasaki, Ken-Ichi Nonomura
The 24-nucleotides (nt) phased secondary small interfering RNA (phasiRNA) is a unique class of plant small RNAs abundantly expressed in monocot anthers at early meiosis. Previously, 44 intergenic regions were identified as the loci for longer precursor RNAs of 24-nt phasiRNAs (24-PHASs) in the rice genome. However, the regulatory mechanism that determines spatiotemporal expression of these RNAs has remained elusive. ETERNAL TAPETUM1 (EAT1) is a basic-helix-loop-helix (bHLH) transcription factor indispensable for induction of programmed cell death (PCD) in postmeiotic anther tapetum, the somatic nursery for pollen production...
February 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29428901/fragile-x-mental-retardation-protein-participates-in-non-coding-rna-pathways
#11
En-Hui Li, Xin Zhao, Ce Zhang, Wei Liu
Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells...
February 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29427099/rna-related-pathology-in-huntington-s-disease
#12
Andreas Neueder, Gillian P Bates
This chapter summarises research investigating the expression of huntingtin sense and anti-sense transcripts, the effect of the mutation on huntingtin processing as well as the more global effect of the mutation on the coding and non-coding transcriptomes. The huntingtin gene is ubiquitously expressed, although expression levels vary between tissues and cell types. A SNP that affects NF-ĸB binding in the huntingtin promoter modulates the expression level of huntingtin transcripts and is associated with the age of disease onset...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29421160/functional-elucidation-of-lvtoll-3-receptor-from-p-vannamei-through-rna-interference-and-its-potential-role-in-the-shrimp-antiviral-response
#13
David Angelo V Guanzon, Mary Beth B Maningas
There is a continuing debate on whether an antiviral immunity similar to vertebrate interferon response exists in invertebrates. Recent advances in penaeid immunology identified several new members of the Toll receptor family and one of these is LvToll3 (Litopenaeus vannamei Toll3). It is hypothesized in this study that LvToll3 responds to pathogen associated molecular patterns (PAMPs) such as dsRNA, which then activates certain antiviral pathways in penaeids. RNA interference (RNAi) was used to determine differences in the expression levels of specific genes putatively involved in the antiviral response through qPCR...
February 5, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29416038/drosha-drives-the-formation-of-dna-rna-hybrids-around-dna-break-sites-to-facilitate-dna-repair
#14
Wei-Ting Lu, Ben R Hawley, George L Skalka, Robert A Baldock, Ewan M Smith, Aldo S Bader, Michal Malewicz, Felicity Z Watts, Ania Wilczynska, Martin Bushell
The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29413516/multiple-pathways-mediate-microrna-degradation-focus-on-the-translin-trax-rnase-complex
#15
Jay M Baraban, Aparna Shah, Xiuping Fu
The discovery of the microRNA system has revolutionized our understanding of translational control. Furthermore, growing appreciation of the pivotal role that de novo translation plays in activity-dependent synaptic plasticity has fueled interest among neuroscientists in deciphering how the microRNA system impacts neuronal signaling and the pathophysiology of neuropsychiatric disorders. Although we have a general understanding of how the microRNA system operates, many key questions remain. In particular, the biosynthesis of microRNAs and their role in translational silencing are fairly well understood...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29411671/mirna-biogenesis-pathway-is-differentially-regulated-during-adipose-derived-stromal-stem-cell-differentiation
#16
E C Martin, A T Qureshi, C B Llamas, M E Burow, A G King, O C Lee, V Dasa, M A Freitas, J A Forsberg, E A Elster, T A Davis, J M Gimble
Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood...
February 7, 2018: Adipocyte
https://www.readbyqxmd.com/read/29408500/microrna-let-7c-5p-improves-neurological-outcomes-in-a-murine-model-of-traumatic-brain-injury-by-suppressing-neuroinflammation-and-regulating-microglial-activation
#17
Jingfang Lv, Yong Zeng, Yu Qian, Jingfei Dong, Zhixiang Zhang, Jianning Zhang
MicroRNAs (miRNAs) are a class of non-coding small RNAs that regulate the expression of target genes. They derive from pre-miRNAs that are enzymatically processed by dicer to ∼22 nucleotide mature miRNAs. Members of the pre-miRNA lethal-7 (let-7) are known to regulate cell proliferation and apoptosis. Here, we showed that the level of let-7c-5p, a key member of the let-7 family, was rapidly reduced in the traumatically injured foci in brains of adult C57BL/6J mice and gradually recovered to the pre-injury level 14 days after traumatic brain injury (TBI) induction...
February 3, 2018: Brain Research
https://www.readbyqxmd.com/read/29405546/detection-of-exogenous-double-stranded-rna-dsrna-movement-in-in-vitro-peanut-plants
#18
Paola C Faustinelli, Imana L Power, Renée S Arias
New technologies are needed to eliminate mycotoxins and/or fungal pathogens from agricultural products. RNA interference (RNAi) has shown potential to control fungi associated with crops. In RNAi, double-stranded RNA (dsRNA) targets homologous mRNA for cleavage, and can reach the mRNA of pathogens in contact with the plant. The key element in this process is the movement of RNA signals cell-to-cell and over long distances within the plant, and between host plants and parasites. In this study, we selected a regulatory gene in the aflatoxin-biosynthesis pathway, aflS/aflR, necessary for the production of aflatoxins in Aspergillus spp...
February 6, 2018: Plant Biology
https://www.readbyqxmd.com/read/29404209/development-of-an-rna-interference-rnai-gene-knockdown-protocol-in-the-anaerobic-gut-fungus-pecoramyces-ruminantium-strain-c1a
#19
Shelby S Calkins, Nicole C Elledge, Katherine E Mueller, Stephen M Marek, M B Couger, Mostafa S Elshahed, Noha H Youssef
Members of the anaerobic gut fungi (AGF) reside in rumen, hindgut, and feces of ruminant and non-ruminant herbivorous mammals and reptilian herbivores. No protocols for gene insertion, deletion, silencing, or mutation are currently available for the AGF, rendering gene-targeted molecular biological manipulations unfeasible. Here, we developed and optimized an RNA interference (RNAi)-based protocol for targeted gene silencing in the anaerobic gut fungus Pecoramyces ruminantium strain C1A. Analysis of the C1A genome identified genes encoding enzymes required for RNA silencing in fungi (Dicer, Argonaute, Neurospora crassa QDE-3 homolog DNA helicase, Argonaute-interacting protein, and Neurospora crassa QIP homolog exonuclease); and the competency of C1A germinating spores for RNA uptake was confirmed using fluorescently labeled small interfering RNAs (siRNA)...
2018: PeerJ
https://www.readbyqxmd.com/read/29402773/protective-effects-of-let-7b-on-the-expression-of-occludin-by-targeting-p38-mapk-in-preventing-intestinal-barrier-dysfunction
#20
Zhihua Liu, Yinghai Tian, Yanqiong Jiang, Shihua Chen, Ting Liu, Mary Pat Moyer, Huanlong Qin, Xinke Zhou
BACKGROUND/AIMS: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. METHODS: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate...
January 19, 2018: Cellular Physiology and Biochemistry
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