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https://www.readbyqxmd.com/read/27930306/mir-17%C3%A2-92-family-clusters-control-inkt-cell-ontogenesis-via-modulation-of-tgf-%C3%AE-signaling
#1
Maya Fedeli, Michela Riba, Jose Manuel Garcia Manteiga, Lei Tian, Valentina Viganò, Grazisa Rossetti, Massimiliano Pagani, Changchun Xiao, Adrian Liston, Elia Stupka, Davide Cittaro, Sergio Abrignani, Paolo Provero, Paolo Dellabona, Giulia Casorati
Invariant natural killer T cells (iNKT) cells are T lymphocytes displaying innate effector functions, acquired through a distinct thymic developmental program regulated by microRNAs (miRNAs). Deleting miRNAs by Dicer ablation (Dicer KO) in thymocytes selectively impairs iNKT cell survival and functional differentiation. To unravel this miRNA-dependent program, we systemically identified transcripts that were differentially expressed between WT and Dicer KO iNKT cells at different differentiation stages and predicted to be targeted by the iNKT cell-specific miRNAs...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929436/comparison-of-small-rna-profiles-of-glycine-max-and-glycine-soja-at-early-developmental-stages
#2
Yuzhe Sun, Zeta Mui, Xuan Liu, Aldrin Kay-Yuen Yim, Hao Qin, Fuk-Ling Wong, Ting-Fung Chan, Siu-Ming Yiu, Hon-Ming Lam, Boon Leong Lim
Small RNAs, including microRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs; from PHAS loci), play key roles in plant development. Cultivated soybean, Glycine max, contributes a great deal to food production, but, compared to its wild kin, Glycine soja, it may lose some genetic information during domestication. In this work, we analyzed the sRNA profiles of different tissues in both cultivated (C08) and wild soybeans (W05) at three stages of development. A total of 443 known miRNAs and 15 novel miRNAs showed varying abundances between different samples, but the miRNA profiles were generally similar in both accessions...
December 6, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27928938/sequence-and-structure-based-analysis-of-proteins-involved-in-mirna-biogenesis
#3
Chhaya Sharma, Debasisa Mohanty
miRNA biogenesis is a multistage process for generation of a mature miRNA and involves several different proteins. In this work, we have carried out sequence as well as structure based analysis for crucial proteins involved in miRNA biogenesis, namely, Dicer, Drosha, Argonaute (Ago) and Exportin-5 to understand evolution of these proteins in animal kingdom and also to identify key sequence and structural features which are determinants of their function. Our analysis reveals that in animals the miRNA biogenesis pathway first originated in molluscs...
December 8, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27928054/the-influence-of-the-5-terminal-nucleotide-on-agoshrna-activity-and-biogenesis-importance-of-the-polymerase-iii-transcription-initiation-site
#4
Elena Herrera-Carrillo, Zong-Liang Gao, Alex Harwig, Matthias T Heemskerk, Ben Berkhout
Recent evidence indicates that shRNAs with a relatively short basepaired stem do not require Dicer processing, but instead are processed by the Argonaute 2 protein (Ago2). We named these molecules AgoshRNAs as both their processing and silencing function are mediated by Ago2. This alternative processing yields only a single RNA guide strand, which can avoid off-target effects induced by the passenger strand of regular shRNAs. It is important to understand this alternative processing route in mechanistic detail such that one can design improved RNA reagents...
December 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27927653/knockdown-of-add3-impairs-the-myogenic-response-of-renal-afferent-arterioles-and-middle-cerebral-arteries
#5
Fan Fan, Mallikarjuna R Pabbidi, Ying Ge, Longyang Li, Shaoxun Wang, Paige N Mims, Richard J Roman
We have reported that the myogenic response of the renal afferent arteriole (Af-art) and middle cerebral artery (MCA), and autoregulation of renal and cerebral blood flow are impaired in Fawn Hood Hypertensive (FHH) rats. Transfer of a region of chromosome 1 containing gamma-adducin (Add3) from Brown Norway rats rescues the vascular dysfunction and the development of renal disease. To examine whether Add3 is a viable candidate gene altering renal and cerebral hemodynamics in FHH rats, we knocked down the expression of Add3 in rat Af-art and MCA cultured for 36-hours using a 27-mer Dicer-substrate short interfering RNA (DsiRNA)...
December 7, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27924483/rapid-generation-of-mirna-inhibitor-leads-by-bioinformatics-and-efficient-high-throughput-screening-methods
#6
Christopher L Haga, Sai Pradeep Velagapudi, Jessica L Childs-Disney, Jacqueline Strivelli, Matthew D Disney, Donald G Phinney
The discovery of microRNAs (miRNAs) has opened an entire new avenue for drug development. These short (15-22 nucleotides) noncoding RNAs, which function in RNA silencing and posttranscriptional regulation of gene expression, have been shown to critically affect numerous pathways in both development and disease progression. Current miRNA drug development focuses on either reintroducing the miRNA into cells through the use of a miRNA mimic or inhibiting its function via use of a synthetic antagomir. Although these methods have shown some success as therapeutics, they face challenges particularly with regard to cellular uptake and for use as systemic reagents...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924480/design-of-multimodal-small-molecules-targeting-mirnas-biogenesis-synthesis-and-in-vitro-evaluation
#7
Duc D Vo, Maria Duca
microRNAs (miRNAs) are emerging as novel biological targets for medicinal chemists to develop chemical tools for intracellular regulation. In this context, the discovery of small-molecule drugs targeting specific miRNAs and modulating their production or function represents a very promising approach that could be further developed for targeted therapy in miRNA-related pathologies. Here, we describe the design of multimodal small molecules as RNA ligands targeting DICER-mediated miRNA maturation. The synthesis and the biochemical evaluation as ligands of stem-loop-structured precursor microRNAs (pre-miRNAs) are reported...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27918527/induction-and-suppression-of-antiviral-rna-interference-by-influenza-a-virus-in-mammalian-cells
#8
Yang Li, Megha Basavappa, Jinfeng Lu, Shuwei Dong, D Alexander Cronkite, John T Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V Karginov, Shou-Wei Ding, Kate L Jeffrey
Influenza A virus (IAV) causes annual epidemics and occasional pandemics, and is one of the best-characterized human RNA viral pathogens(1). However, a physiologically relevant role for the RNA interference (RNAi) suppressor activity of the IAV non-structural protein 1 (NS1), reported over a decade ago(2), remains unknown(3). Plant and insect viruses have evolved diverse virulence proteins to suppress RNAi as their hosts produce virus-derived small interfering RNAs (siRNAs) that direct specific antiviral defence(4-7) by an RNAi mechanism dependent on the slicing activity of Argonaute proteins (AGOs)(8,9)...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27915033/survivin-controls-biogenesis-of-microrna-in-smokers-a-link-to-pathogenesis-of-rheumatoid-arthritis
#9
Karin M E Andersson, Minna Turkkila, Malin C Erlandsson, Apostolos Bossios, Sofia Töyrä Silfverswärd, Dan Hu, Linda Ekerljung, Carina Malmhäll, Howard L Weiner, Bo Lundbäck, Maria I Bokarewa
MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms...
November 30, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27907832/modeling-of-the-catalytic-core-of-arabidopsis-thaliana-dicer-like-4-protein-and-its-complex-with-double-stranded-rna
#10
Agnieszka Mickiewicz, Joanna Sarzyńska, Maciej Miłostan, Anna Kurzyńska-Kokorniak, Agnieszka Rybarczyk, Piotr Łukasiak, Tadeusz Kuliński, Marek Figlerowicz, Jacek Błażewicz
Plant Dicer-like proteins (DCLs) belong to the Ribonuclease III (RNase III) enzyme family. They are involved in the regulation of gene expression and antiviral defense through RNA interference pathways. A model plant, Arabidopsis thaliana encodes four DCL proteins (AtDCL1-4) that produce different classes of small regulatory RNAs. Our studies focus on AtDCL4 that processes double-stranded RNAs (dsRNAs) into 21 nucleotide trans-acting small interfering RNAs. So far, little is known about the structures of plant DCLs and the complexes they form with dsRNA...
November 17, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27901078/asian-citrus-psyllid-rnai-pathway-rnai-evidence
#11
Clauvis N T Taning, Eduardo C Andrade, Wayne B Hunter, Olivier Christiaens, Guy Smagghe
Diaphorina citri, known as the Asian citrus psyllid, is an important pest of citrus because it transmits a phloem-limited bacteria strongly implicated in huanglongbing (citrus greening disease). Emerging biotechnologies, such as RNA interference, could provide a new sustainable and environmentally friendly strategy for the management of this pest. In this study, genome and functional analysis were performed to verify whether the RNAi core genes are present in the Asian psyllid genome and if the RNAi machinery could be exploited to develop a management strategy for this pest...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900550/biogenesis-of-diverse-plant-phasirnas-involves-an-mirna-trigger-and-dicer-processing
#12
Reina Komiya
It has been almost 30 years since RNA interference (RNAi) was shown to silence genes via double-stranded RNAs (dsRNAs) in Caenorhabditis elegans (Fire et al. 1998). 20-30-nucleotide (nt) small non-coding RNAs are a key element of the RNAi machinery. Recently, phased small interfering RNAs (phasiRNAs), small RNAs that are generated from a long RNA precursor at intervals of 21 to 26-nt, have been identified in plants and animals. In Drosophila, phasiRNAs are generated by the endonuclease, Zucchini (Zuc), in germlines...
November 29, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27893764/virus-mediated-alterations-in-mirna-factors-and-degradation-of-viral-mirnas-by-mcpip1
#13
Christine Happel, Dhivya Ramalingam, Joseph M Ziegelbauer
Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a critical regulator of immune homeostasis, has been shown to suppress miRNA biosynthesis via cleavage of precursor miRNAs through its RNase domain. We demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and that MCPIP1 expression is repressed following de novo KSHV infection. In addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6 and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA regulation...
November 2016: PLoS Biology
https://www.readbyqxmd.com/read/27887571/lbsizecleav-improved-support-vector-machine-svm-based-prediction-of-dicer-cleavage-sites-using-loop-bulge-length
#14
Yu Bao, Morihiro Hayashida, Tatsuya Akutsu
BACKGROUND: Dicer is necessary for the process of mature microRNA (miRNA) formation because the Dicer enzyme cleaves pre-miRNA correctly to generate miRNA with correct seed regions. Nonetheless, the mechanism underlying the selection of a Dicer cleavage site is still not fully understood. To date, several studies have been conducted to solve this problem, for example, a recent discovery indicates that the loop/bulge structure plays a central role in the selection of Dicer cleavage sites...
November 25, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/27885505/pre-microrna-processing-activity-in-nuclear-extracts-from-arabidopsis-suspension-cells
#15
Manabu Yoshikawa
MicroRNAs (miRNAs) play important roles in a variety of biological phenomena, such as development and responses to abiotic and biotic stresses, by regulating complementary target transcripts. Primary MIRNA transcripts (pri-miRNAs) are processed into miRNA/miRNA* duplexes via pre-miRNA intermediates by DICER family proteins. In plants miRNA/miRNA* duplexes are produced from pri-miRNAs exclusively by a complex containing DICER-LIKE1 (DCL1), Hyponastic leaves1 (HYL1) and SERREATE (SE) in the nucleus. Pri-miRNA or pre-miRNA processing activity has been detected using recombinant DCL1, HYL1 and SE proteins expressed in insect cells and immunopurified DCL1-HYL1-SE-containing complexes that transiently co-overexpressed in Nicotiana benthamiana...
November 24, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27885504/plant-dicer-like-proteins-double-stranded-rna-cleaving-enzymes-for-small-rna-biogenesis
#16
Akihito Fukudome, Toshiyuki Fukuhara
Dicer, a double-stranded RNA (dsRNA)-specific endoribonuclease, plays an essential role in triggering both transcriptional and post-transcriptional gene silencing in eukaryotes by cleaving dsRNAs or single-stranded RNAs bearing stem-loop structures such as microRNA precursor transcripts into 21- to 24-nt small RNAs. Unlike animals, plants have evolved to utilize at least four Dicer-like (DCL) proteins. Extensive genetic studies have revealed that each DCL protein participates in a specific gene silencing pathway, with some redundancy...
November 24, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27880894/requirement-for-dicer-in-maintenance-of-monosynaptic-sensory-motor-circuits-in-the-spinal-cord
#17
Fumiyasu Imai, Xiaoting Chen, Matthew T Weirauch, Yutaka Yoshida
In contrast to our knowledge of mechanisms governing circuit formation, our understanding of how neural circuits are maintained is limited. Here, we show that Dicer, an RNaseIII protein required for processing microRNAs (miRNAs), is essential for maintenance of the spinal monosynaptic stretch reflex circuit in which group Ia proprioceptive sensory neurons form direct connections with motor neurons. In postnatal mice lacking Dicer in proprioceptor sensory neurons, there are no obvious defects in specificity or formation of monosynaptic sensory-motor connections...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27872619/ebola-vp40-in-exosomes-can-cause-immune-cell-dysfunction
#18
Michelle L Pleet, Allison Mathiesen, Catherine DeMarino, Yao A Akpamagbo, Robert A Barclay, Angela Schwab, Sergey Iordanskiy, Gavin C Sampey, Benjamin Lepene, Sergei Nekhai, M J Aman, Fatah Kashanchi
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27872309/phosphate-binding-pocket-in-dicer-2-paz-domain-for-high-fidelity-sirna-production
#19
Suresh K Kandasamy, Ryuya Fukunaga
The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ∼22-24-nt miRNAs from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high fidelity is unknown. Here we report that recognition of the 5'-monophosphate of a long dsRNA substrate by a phosphate-binding pocket in the Dicer-2 PAZ (Piwi, Argonaute, and Zwille/Pinhead) domain is crucial for the length fidelity, but not the efficiency, in 21-nt siRNA production...
December 6, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27856616/antisense-transcription-licenses-nascent-transcripts-to-mediate-transcriptional-gene-silencing
#20
Yunkun Dang, Jiasen Cheng, Xianyun Sun, Zhipeng Zhou, Yi Liu
In eukaryotes, antisense transcription can regulate sense transcription by induction of epigenetic modifications. We showed previously that antisense transcription triggers Dicer-independent siRNA (disiRNA) production and disiRNA locus DNA methylation (DLDM) in Neurospora crassa Here we show that the conserved exonuclease ERI-1 (enhanced RNAi-1) is a critical component in this process. Antisense transcription and ERI-1 binding to target RNAs are necessary and sufficient to trigger DLDM. Convergent transcription causes stalling of RNA polymerase II during transcription, which permits ERI-1 to bind nascent RNAs in the nucleus and recruit a histone methyltransferase complex that catalyzes chromatin modifications...
November 17, 2016: Genes & Development
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