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https://www.readbyqxmd.com/read/28319084/structural-and-mechanistic-insights-into-an-archaeal-dna-guided-argonaute-protein
#1
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
#2
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
#3
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-md-simulations
#4
Sekarjayanthan Harikrishna, Pushpangadan Indira 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 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 13, 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
#5
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
#6
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
https://www.readbyqxmd.com/read/28262506/autonomous-generation-and-loading-of-dna-guides-by-bacterial-argonaute
#7
Daan C Swarts, Malwina Szczepaniak, Gang Sheng, Stanley D Chandradoss, Yifan Zhu, Elizabeth M Timmers, Yong Zhang, Hongtu Zhao, Jizhong Lou, Yanli Wang, Chirlmin Joo, John van der Oost
Several prokaryotic Argonaute proteins (pAgos) utilize small DNA guides to mediate host defense by targeting invading DNA complementary to the DNA guide. It is unknown how these DNA guides are being generated and loaded onto pAgo. Here, we demonstrate that guide-free Argonaute from Thermus thermophilus (TtAgo) can degrade double-stranded DNA (dsDNA), thereby generating small dsDNA fragments that subsequently are loaded onto TtAgo. Combining single-molecule fluorescence, molecular dynamic simulations, and structural studies, we show that TtAgo loads dsDNA molecules with a preference toward a deoxyguanosine on the passenger strand at the position opposite to the 5' end of the guide strand...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28243313/utilizing-selected-di-and-trinucleotides-of-sirna-to-predict-rnai-activity
#8
Ye Han, Yuanning Liu, Hao Zhang, Fei He, Chonghe Shu, Liyan Dong
Small interfering RNAs (siRNAs) induce posttranscriptional gene silencing in various organisms. siRNAs targeted to different positions of the same gene show different effectiveness; hence, predicting siRNA activity is a crucial step. In this paper, we developed and evaluated a powerful tool named "siRNApred" with a new mixed feature set to predict siRNA activity. To improve the prediction accuracy, we proposed 2-3NTs as our new features. A Random Forest siRNA activity prediction model was constructed using the feature set selected by our proposed Binary Search Feature Selection (BSFS) algorithm...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/28240212/-are-the-argonauts-lost-at-sea
#9
Bertrand Jordan
A novel gene editing procedure based on a nuclease from the Argonaute protein family was described in mid-2016 and appeared to provide significant advantages over the now widely used CRISPR-Cas9 system. Attempts by numerous groups to use this technique have however been unsuccessful; several negative reports have been published in addition to many accounts of failure found in the "grey literature". It is unclear at this point whether this reflects an (unknown) critical experimental factor or hints at data misinterpretation, possibly even at outright fabrication of results...
February 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28239561/regulation-of-cardiac-cacnb2-by-microrna-499-potential-role-in-atrial-fibrillation
#10
Tian-You Ling, Xiao-Li Wang, Qiang Chai, Tong Lu, John M Stulak, Lyle D Joyce, Richard C Daly, Kevin L Greason, Li-Qun Wu, Win-Kuang Shen, Yong-Mei Cha, Hon-Chi Lee
The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28231321/argonaute10-promotes-the-degradation-of-mir165-6-through-the-sdn1-and-sdn2-exonucleases-in-arabidopsis
#11
Yu Yu, Lijuan Ji, Brandon H Le, Jixian Zhai, Jiayi Chen, Elizabeth Luscher, Lei Gao, Chunyan Liu, Xiaofeng Cao, Beixin Mo, Jinbiao Ma, Blake C Meyers, Xuemei Chen
The degradation of small RNAs in plants and animals is associated with small RNA 3' truncation and 3' uridylation and thus relies on exonucleases and nucleotidyl transferases. ARGONAUTE (AGO) proteins associate with small RNAs in vivo and are essential for not only the activities but also the stability of small RNAs. AGO1 is the microRNA (miRNA) effector in Arabidopsis, and its closest homolog, AGO10, maintains stem cell homeostasis in meristems by sequestration of miR165/6, a conserved miRNA acting through AGO1...
February 2017: PLoS Biology
https://www.readbyqxmd.com/read/28228545/ablation-of-rnai-and-retrotransposons-accompany-acquisition-and-evolution-of-transposases-to-heterochromatin-protein-cenpb
#12
Udita Upadhyay, Suchita Srivastava, Indu Khatri, Jagpreet Singh Nanda, Srikrishna Subramanian, Amit Arora, Jagmohan Singh
Inactivation of retrotransposons is accompanied by the emergence of CENPB (centromere binding protein-B) in Schizosaccharomyces as well as in metazoans. The RNAi-induced Transcriptional Silencing (RITS) Complex, comprising Chp1 (chromodomain protein-1), Tas3 (protein with unknown function) and Ago1 (Argonaute), plays an important role in RNAi-mediated heterochromatinization. We find that while the Ago1 subunit of the RITS complex is highly conserved, Tas3 is lost and Chp1 is truncated in S. cryophilus and S...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228216/non-canonical-targets-play-an-important-role-in-mirna-stability-control-mechanism
#13
June Hyun Park, Chanseok Shin
MicroRNAs (miRNAs) regulate gene expression by guiding Argonaute (Ago) containing RNA-induced silencing complex (RISC) to specific target mRNA molecules. It is well established that miRNAs are stabilized by Ago proteins, but the molecular features that triggers miRNA destabilization from Ago proteins remain largely unknown. To explore the molecular mechanisms of how targets affect the stability of miRNAs in human Ago (hAgo) proteins, we employed an in vitro system that consists of a minimal hAgo2-RISC in HEK293T cell lysates...
February 23, 2017: BMB Reports
https://www.readbyqxmd.com/read/28223504/transcriptome-wide-microrna-and-target-dynamics-in-the-fat-body-during-the-gonadotrophic-cycle-of-aedes-aegypti
#14
Xiufeng Zhang, Emre Aksoy, Thomas Girke, Alexander S Raikhel, Fedor V Karginov
The mosquito Aedes aegypti is a major vector of numerous viral diseases, because it requires a blood meal to facilitate egg development. The fat body, a counterpart of mammalian liver and adipose tissues, is the metabolic center, playing a key role in reproduction. Therefore, understanding of regulatory networks controlling its functions is critical, and the role of microRNAs (miRNAs) in the process is largely unknown. We aimed to explore miRNA expression and potential targets in the female fat body of Ae. aegypti, as well as their changes postblood meal (PBM)...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223440/idn2-interacts-with-rpa-and-facilitates-dna-double-strand-break-repair-by-homologous-recombination-in-arabidopsis
#15
Mingming Liu, Zhaoqing Ba, Pedro Costa-Nunes, Wei Wei, Lanxia Li, Fansi Kong, Yan Li, Jijie Chai, Olga Pontes, Yijun Qi
Repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genome integrity. We previously showed that DSB-induced small RNAs (diRNAs) facilitate homologous recombination (HR)-mediated DSB repair in Arabidopsis thaliana. Here we show that INVOLVED IN DE NOVO 2 (IDN2), a double-stranded RNA (dsRNA) binding protein involved in small RNA-directed DNA methylation, is required for DSB repair in Arabidopsis. We find that IDN2 interacts with the heterotrimeric replication protein A (RPA) complex...
February 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28210761/the-evolutionary-loss-of-rnai-key-determinants-in-kinetoplastids-as-a-multiple-sporadic-phenomenon
#16
Andrey V Matveyev, João M P Alves, Myrna G Serrano, Vladimir Lee, Ana M Lara, William A Barton, André G Costa-Martins, Stephen M Beverley, Erney P Camargo, Marta M G Teixeira, Gregory A Buck
We screened the genomes of a broad panel of kinetoplastid protists for genes encoding proteins associated with the RNA interference (RNAi) system using probes from the Argonaute (AGO1), Dicer1 (DCL1), and Dicer2 (DCL2) genes of Leishmania brasiliensis and Crithidia fasciculata. We identified homologs for all the three of these genes in the genomes of a subset of these organisms. However, several of these organisms lacked evidence for any of these genes, while others lacked only DCL2. The open reading frames encoding these putative proteins were structurally analyzed in silico...
February 16, 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/28206606/the-small-non-coding-rna-processing-machinery-of-two-living-fossil-species-lungfish-and-coelacanth-gives-new-insights-into-the-evolution-of-the-argonaute-protein-family
#17
Biscotti Maria Assunta, Canapa Adriana, Forconi Mariko, Gerdol Marco, Pallavicini Alberto, Schartl Manfred, Barucca Marco
No abstract text is available yet for this article.
February 16, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28198592/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#18
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
February 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28187792/evolution-of-rna-and-dna-guided-antivirus-defense-systems-in-prokaryotes-and-eukaryotes-common-ancestry-vs-convergence
#19
REVIEW
Eugene V Koonin
Complementarity between nucleic acid molecules is central to biological information transfer processes. Apart from the basal processes of replication, transcription and translation, complementarity is also employed by multiple defense and regulatory systems. All cellular life forms possess defense systems against viruses and mobile genetic elements, and in most of them some of the defense mechanisms involve small guide RNAs or DNAs that recognize parasite genomes and trigger their inactivation. The nucleic acid-guided defense systems include prokaryotic Argonaute (pAgo)-centered innate immunity and CRISPR-Cas adaptive immunity as well as diverse branches of RNA interference (RNAi) in eukaryotes...
February 10, 2017: Biology Direct
https://www.readbyqxmd.com/read/28186701/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#20
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
January 26, 2017: Stem Cells Translational Medicine
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