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https://www.readbyqxmd.com/read/28423324/resolving-subcellular-mirna-trafficking-and-turnover-at-single-molecule-resolution
#1
Sethuramasundaram Pitchiaya, Laurie A Heinicke, Jun I Park, Elizabeth L Cameron, Nils G Walter
Regulation of microRNA (miRNA) localization and stability is critical for their extensive cytoplasmic RNA silencing activity and emerging nuclear functions. Here, we have developed single-molecule fluorescence-based tools to assess the subcellular trafficking, integrity, and activity of miRNAs. We find that seed-matched RNA targets protect miRNAs against degradation and enhance their nuclear retention. While target-stabilized, functional, cytoplasmic miRNAs reside in high-molecular-weight complexes, nuclear miRNAs, as well as cytoplasmic miRNAs targeted by complementary anti-miRNAs, are sequestered stably within significantly lower-molecular-weight complexes and rendered repression incompetent...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28404517/dysregulation-of-microrna-biogenesis-in-the-small-intestine-after-ethanol-and-burn-injury
#2
Niya L Morris, Adam M Hammer, Abigail R Cannon, Robin C Gagnon, Xiaoling Li, Mashkoor A Choudhry
Ethanol exposure at the time of burn injury is a major contributor to post-burn pathogenesis. Many of the adverse effects associated with ethanol and burn injury are linked to an impaired intestinal barrier. The combined insult causes intestinal inflammation, resulting in tissue damage, altered tight junction expression, and increased intestinal permeability. MicroRNAs play a critical role in maintaining intestinal homeostasis including intestinal inflammation and barrier function. Specifically, miR-150 regulates inflammatory mediators which can contribute to gut barrier disruption...
April 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28403818/srnas-as-possible-regulators-of-retrotransposon-activity-in-cryptococcus-gattii-vgii
#3
Patrícia Aline Gröhs Ferrareze, Rodrigo Silva Araujo Streit, Francine Melise Dos Santos, Augusto Schrank, Livia Kmetzsch, Marilene Henning Vainstein, Charley Christian Staats
BACKGROUND: The absence of Argonaute genes in the fungal pathogen Cryptococcus gattii R265 and other VGII strains indicates that yeasts of this genotype cannot have a functional RNAi pathway, an evolutionarily conserved gene silencing mechanism performed by small RNAs. The success of the R265 strain as a pathogen that caused the Pacific Northwest and Vancouver Island outbreaks may imply that RNAi machinery loss could be beneficial under certain circumstances during evolution. As a result, a hypermutant phenotype would be created with high rates of genome retrotransposition, for instance...
April 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28400515/saga-complex-mediates-the-transcriptional-up-regulation-of-antiviral-rna-silencing
#4
Ida Bagus Andika, Atif Jamal, Hideki Kondo, Nobuhiro Suzuki
Pathogen recognition and transcriptional activation of defense-related genes are crucial steps in cellular defense responses. RNA silencing (RNAi) functions as an antiviral defense in eukaryotic organisms. Several RNAi-related genes are known to be transcriptionally up-regulated upon virus infection in some host organisms, but little is known about their induction mechanism. A phytopathogenic ascomycete, Cryphonectria parasitica (chestnut blight fungus), provides a particularly advantageous system to study RNAi activation, because its infection by certain RNA viruses induces the transcription of dicer-like 2 (dcl2) and argonaute-like 2 (agl2), two major RNAi players...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28388001/exploring-the-rna-bound-and-rna-free-human-argonaute-2-by-molecular-dynamics-simulation-method
#5
Ren Kong, Lei Xu, Lianhua Piao, Dawei Zhang, Ting-Jun Hou, Shan Chang
Argonaute 2 (Ago2) protein is the major vehicle of MicroRNAs (miRNAs) guided gene repression and silencing processes. Although the crystal structure of human Ago2 (hAgo2) has recently been disclosed but the information of dynamically structural character of protein-RNA recognition is still lacking. Molecular dynamics simulations were used to systematically explore hAgo2 in the presence and absence of RNA duplex. Stable direct and water-mediated hydrogen bonds were observed between guide RNA backbone atoms and hAgo2, especially for nucleotides 2-7...
April 7, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28381556/poly-c-binding-protein-1-pcbp1-regulates-skeletal-muscle-differentiation-by-modulating-microrna-processing-in-myoblasts
#6
Ramon A Espinoza-Lewis, Qiumei Yang, Jianming Liu, Zhan-Peng Huang, Xiaoyun Hu, Daiwen Chen, Da-Zhi Wang
Control of muscle cell proliferation and differentiation is essential to proper muscle development, function, and regeneration, and numerous transcriptional and post-transcriptional regulators are key to these processes. For example, recent studies have linked microRNAs (miRNAs) to muscle gene expression, development, and disease. The poly(C)-binding protein1 (Pcbp1, hnRNP-E1, or αCP-1) has been reported to bind the 3'UTRs of target genes to regulate mRNA stability and protein translation. However, Pcbp1's biological function in skeletal muscle and general mechanism of action remain largely undetermined...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28351993/mutations-in-argonaute5-illuminate-epistatic-interactions-of-the-k1-and-i-loci-leading-to-saddle-seed-color-patterns-in-glycine-max
#7
Young B Cho, Sarah I Jones, Lila O Vodkin
The soybean (Glycine max) seed coat has distinctive, genetically programmed patterns of pigmentation and the recessive k1 mutation can epistatically overcome the dominant I and ii alleles, which inhibit seed color by producing small interfering RNAs (siRNAs) targeting chalcone synthase (CHS) mRNAs. Small RNA sequencing of dissected regions of immature seed coats demonstrated that CHS siRNA levels cause the patterns produced by the ii and ik alleles of the I locus, which restrict pigment to the hilum or saddle region of the seed coat, respectively...
March 28, 2017: Plant Cell
https://www.readbyqxmd.com/read/28349357/characterization-of-sirnas-derived-from-cucumber-mosaic-virus-in-infected-tobacco-plants
#8
Yanhong Qiu, Yongjiang Zhang, Fan Hu, Shuifang Zhu
This study characterized the viral small interfering RNAs (vsiRNAs) from Nicotiana tabacum cv. Samsun infected with a cucumber mosaic virus (CMV) 2b-deficient mutant. Most vsiRNAs were 21 -22 nucleotides in length and the 5'-terminal ends were dominated by A and U, respectively. The observed vsiRNAs were heterogeneously distributed throughout the CMV genome; however, most of the vsiRNAs were derived from sense strands, as opposed to antisense strands. These results demonstrate the conserved and specific function of Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) proteins in tobacco...
March 27, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28343968/met-2-dependent-h3k9-methylation-suppresses-transgenerational-small-rna-inheritance
#9
Itamar Lev, Uri Seroussi, Hila Gingold, Roberta Bril, Sarit Anava, Oded Rechavi
In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs...
March 21, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28338719/the-legume-mir1514a-modulates-a-nac-transcription-factor-transcript-to-trigger-phasirna-formation-in-response-to-drought
#10
Guadalupe Sosa-Valencia, Miguel Palomar, Alejandra A Covarrubias, José L Reyes
Recent studies have identified microRNAs as post-transcriptional regulators involved in stress responses. miR1514a is a legume microRNA that is induced in response to drought stress in Phaseolus vulgaris (common bean) and shows differential accumulation levels in roots during water deficit in two cultivars with different drought tolerance phenotypes. A recent degradome analysis revealed that miR1514a targets the transcripts of two NAC transcription factors (TFs), Phvul.010g121000 and Phvul.010g120700. Furthermore, expression studies and small RNA-seq data indicate that only Phvul...
October 7, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28334969/a-single-mir390-targeting-event-is-sufficient-for-triggering-tas3-tasirna-biogenesis-in-arabidopsis
#11
Felipe Fenselau de Felippes, Antonin Marchais, Alexis Sarazin, Stefan Oberlin, Olivier Voinnet
In plants, tasiRNAs form a class of endogenous secondary siRNAs produced through the action of RNA-DEPENDENT-RNA-POLYMERASE-6 (RDR6) upon microRNA-mediated cleavage of non-coding TAS RNAs. In Arabidopsis thaliana, TAS1, TAS2 and TAS4 tasiRNA production proceeds via a single cleavage event mediated by 22nt-long or/and asymmetric miRNAs in an ARGONAUTE-1 (AGO1)-dependent manner. By contrast, tasiRNA production from TAS3 seems to follow the so-called 'two-hit' process, where dual targeting of TAS3, specifically mediated by the 21nt-long, symmetric miR390, initiates AGO7-dependent tasiRNA production...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334781/auf1-facilitates-microrna-mediated-gene-silencing
#12
Kyung-Won Min, Myung Hyun Jo, Soochul Shin, Sylvia Davila, Richard W Zealy, Soo Im Kang, Lawson T Lloyd, Sungchul Hohng, Je-Hyun Yoon
Eukaryotic mRNA decay is tightly modulated by RNA-binding proteins (RBPs) and microRNAs (miRNAs). RBP AU-binding factor 1 (AUF1) has four isoforms resulting from alternative splicing and is critical for miRNA-mediated gene silencing with a distinct preference of target miRNAs. Previously, we have shown that AUF1 facilitates miRNA loading to Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex. Here, we further demonstrate that depletion of AUF1 abolishes the global interaction of miRNAs and AGO2...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28331089/diversity-distribution-and-evolution-of-tomato-viruses-in-china-uncovered-by-small-rna-sequencing
#13
Chenxi Xu, Xuepeng Sun, Angela Taylor, Chen Jiao, Yimin Xu, Xiaofeng Cai, Xiaoli Wang, Chenhui Ge, Guanghui Pan, Quanxi Wang, Zhangjun Fei, Quanhua Wang
Tomato is a major vegetable crop that has tremendous popularity. However, viral disease is still a major factor limiting tomato production. Here we report the tomato virome identified through sequencing small RNAs of 170 field-grown samples collected in China. A total of 22 viruses were identified including both well-documented and newly detected viruses. The tomato viral community is dominated by a few species, and they exhibit polymorphisms and recombination in the genomes with coldspots and hotspots. Most samples were co-infected by multiple viruses and the majority of identified viruses are positive-sense single-stranded RNA viruses...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28325872/small-rna-mediated-repair-of-uv-induced-dna-lesions-by-the-dna-damage-binding-protein-2-and-argonaute-1
#14
Catherine Schalk, Valérie Cognat, Stéfanie Graindorge, Timothée Vincent, Olivier Voinnet, Jean Molinier
As photosynthetic organisms, plants need to prevent irreversible UV-induced DNA lesions. Through an unbiased, genome-wide approach, we have uncovered a previously unrecognized interplay between Global Genome Repair and small interfering RNAs (siRNAs) in the recognition of DNA photoproducts, prevalently in intergenic regions. Genetic and biochemical approaches indicate that, upon UV irradiation, the DNA DAMAGE-BINDING PROTEIN 2 (DDB2) and ARGONAUTE 1 (AGO1) of Arabidopsis thaliana form a chromatin-bound complex together with 21-nt siRNAs, which likely facilitates recognition of DNA damages in an RNA/DNA complementary strand-specific manner...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28319084/structural-and-mechanistic-insights-into-an-archaeal-dna-guided-argonaute-protein
#15
Sarah Willkomm, Christine A Oellig, Adrian Zander, Tobias Restle, Ronan Keegan, Dina Grohmann, Sabine Schneider
Argonaute (Ago) proteins in eukaryotes are known as key players in post-transcriptional gene silencing(1), while recent studies on prokaryotic Agos hint at their role in the protection against invading DNA(2,3). Here, we present crystal structures of the apo enzyme and a binary Ago-guide complex of the archaeal Methanocaldococcus jannaschii (Mj) Ago. Binding of a guide DNA leads to large structural rearrangements. This includes the structural transformation of a hinge region containing a switch helix, which has been shown for human Ago2 to be critical for the dynamic target search process(4-6)...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28319081/guide-independent-dna-cleavage-by-archaeal-argonaute-from-methanocaldococcus-jannaschii
#16
Adrian Zander, Sarah Willkomm, Sapir Ofer, Marleen van Wolferen, Luisa Egert, Sabine Buchmeier, Sarah Stöckl, Philip Tinnefeld, Sabine Schneider, Andreas Klingl, Sonja-Verena Albers, Finn Werner, Dina Grohmann
Prokaryotic Argonaute proteins acquire guide strands derived from invading or mobile genetic elements, via an unknown pathway, to direct guide-dependent cleavage of foreign DNA. Here, we report that Argonaute from the archaeal organism Methanocaldococcus jannaschii (MjAgo) possesses two modes of action: the canonical guide-dependent endonuclease activity and a non-guided DNA endonuclease activity. The latter allows MjAgo to process long double-stranded DNAs, including circular plasmid DNAs and genomic DNAs...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28306508/prokaryotic-argonaute-uses-an-all-in-one-mechanism-to-provide-host-defense
#17
Dipali G Sashital
In this issue, Swarts et al. (2017) discover that prokaryotic Argonaute proteins generate their own DNA guide strands through a newly characterized, unguided "chopping" activity. Double-stranded chopping products are selectively loaded onto Argonaute, enabling DNA-guided defense against foreign DNA.
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28287733/probing-the-binding-interactions-between-chemically-modified-sirnas-and-human-argonaute-2-using-microsecond-molecular-dynamics-simulations
#18
S Harikrishna, P I Pradeepkumar
The use of chemical modifications in small interfering RNAs (siRNAs) is warranted to impart drug-like properties. However, certain chemical modifications especially those on the sugar have deleterious effects on the RNA interference (RNAi) when they are placed at key positions in the seed region of an siRNA guide strand. In order to probe the effect of chemically modified siRNAs [(2'-O-methyl, 4'-C-aminomethyl-2'-O-methyl, 2'-O-(2-methoxyethyl), and 2'-O-benzyl] on human Argonaute 2 (hAGO2), the catalytic engine of RNAi, we have developed a model of its open conformation...
March 27, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28270624/abscisic-acid-induces-resistance-against-bamboo-mosaic-virus-through-argonaute-2-and-3
#19
Mazen Alazem, Meng-Hsun He, Peter Moffett, Na-Sheng Lin
Plant resistance to pathogens is tuned by defense-related hormones. Of which, ABA is well documented to moderate resistance against fungi and bacteria. However, ABA's contribution to resistance against viruses is pleiotropic. ABA affects callose deposition at plasmodesmata (therefore hindering the viral cell-to-cell movement), but here we show that when callose synthase is downregulated, ABA still induces resistance against Bamboo mosaic virus (BaMV) infection. By examining the potential connections between the ABA and RNA silencing pathway in Arabidopsis, we showed that ABA regulates the expression of almost the whole Argonaute (AGO) gene family, of which some are required for plant resistance against BaMV...
March 7, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28266707/the-agotrons-gene-regulators-or-argonaute-protectors
#20
REVIEW
Lotte V W Stagsted, Iben Daugaard, Thomas B Hansen
Over the last decades, it has become evident that highly complex networks of regulators govern post-transcriptional regulation of gene expression. A novel class of Argonaute (Ago)-associated RNA molecules, the agotrons, was recently shown to function in a Drosha- and Dicer-independent manner, hence bypassing the maturation steps required for canonical microRNA (miRNA) biogenesis. Agotrons are found in most mammals and associate with Ago as ∼100 nucleotide (nt) long RNA species. Here, we speculate on the functional and biological relevance of agotrons: (i) agotrons could serve as non-promiscuous miRNA-like regulators with reduced off-targeting or (ii) agotrons could encompass other putative functions, such as protecting Ago proteins from taking up aberrant short RNAs or by rescuing and stabilizing otherwise unloaded Ago-proteins from degradation...
March 7, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
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