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https://www.readbyqxmd.com/read/28911094/structure-cleavage-based-insights-into-helical-perturbations-at-bulge-sites-within-t-thermophilus-argonaute-silencing-complexes
#1
Gang Sheng, Tasos Gogakos, Jiuyu Wang, Hongtu Zhao, Artem Serganov, Stefan Juranek, Thomas Tuschl, Dinshaw J Patel, Yanli Wang
We have undertaken a systematic structural study of Thermus thermophilus Argonaute (TtAgo) ternary complexes containing single-base bulges positioned either within the seed segment of the guide or target strands and at the cleavage site. Our studies establish that single-base bulges 7T8, 5A6 and 4A5 on the guide strand are stacked-into the duplex, with conformational changes localized to the bulge site, thereby having minimal impact on the cleavage site. By contrast, single-base bulges 6'U7' and 6'A7' on the target strand are looped-out of the duplex, with the resulting conformational transitions shifting the cleavable phosphate by one step...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28905147/evaluation-and-control-of-mirna-like-off-target-repression-for-rna-interference
#2
REVIEW
Heeyoung Seok, Haejeong Lee, Eun-Sook Jang, Sung Wook Chi
RNA interference (RNAi) has been widely adopted to repress specific gene expression and is easily achieved by designing small interfering RNAs (siRNAs) with perfect sequence complementarity to the intended target mRNAs. Although siRNAs direct Argonaute (Ago), a core component of the RNA-induced silencing complex (RISC), to recognize and silence target mRNAs, they also inevitably function as microRNAs (miRNAs) and suppress hundreds of off-targets. Such miRNA-like off-target repression is potentially detrimental, resulting in unwanted toxicity and phenotypes...
September 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28903378/ago2-involves-the-malignant-phenotypes-and-fak-pi3k-akt-signaling-pathway-in-hypopharyngeal-derived-fadu-cells
#3
Yanhui Zhang, Baoxin Wang, Xinwei Chen, Weidong Li, Pin Dong
Argonaute 2 (AGO2) protein is usually overexpressed in various head and neck squamous cell carcinoma. However, the precise molecular mechanisms of AGO2 in hypopharyngeal cancer have not yet been clearly understood. Here we found the AGO2 expression in hypopharyngeal cancer tissues were generally higher comparing with that of the corresponding adjacent noncancerous epithelium tissues, and these were associated with the more aggressive clinicopathologic features and the poor clinical outcomes. Stable knockdown of AGO2 protein retarded cell proliferation, migration, invasion, arrested cell cycle and induced apoptosis...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903034/piwi-is-required-to-limit-exhaustion-of-aging-somatic-stem-cells
#4
Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T Madden, Victoria V Lunyak, Heinrich Jasper
Sophisticated mechanisms that preserve genome integrity are critical to ensure the maintenance of regenerative capacity while preventing transformation of somatic stem cells (SCs), yet little is known about mechanisms regulating genome maintenance in these cells. Here, we show that intestinal stem cells (ISCs) induce the Argonaute family protein Piwi in response to JAK/STAT signaling during acute proliferative episodes. Piwi function is critical to ensure heterochromatin maintenance, suppress retrotransposon activation, and prevent DNA damage in homeostasis and under regenerative pressure...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28893179/conservation-and-diversification-of-small-rna-pathways-within-flatworms
#5
Santiago Fontenla, Gabriel Rinaldi, Pablo Smircich, Jose F Tort
BACKGROUND: Small non-coding RNAs, including miRNAs, and gene silencing mediated by RNA interference have been described in free-living and parasitic lineages of flatworms, but only few key factors of the small RNA pathways have been exhaustively investigated in a limited number of species. The availability of flatworm draft genomes and predicted proteomes allowed us to perform an extended survey of the genes involved in small non-coding RNA pathways in this phylum. RESULTS: Overall, findings show that the small non-coding RNA pathways are conserved in all the analyzed flatworm linages; however notable peculiarities were identified...
September 11, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28882451/development-and-mechanism-of-small-activating-rna-targeting-cebpa-a-novel-therapeutic-in-clinical-trials-for-liver-cancer
#6
Jon Voutila, Vikash Reebye, Thomas C Roberts, Pantelitsa Protopapa, Pinelopi Andrikakou, David C Blakey, Robert Habib, Hans Huber, Pal Saetrom, John J Rossi, Nagy A Habib
Small activating RNAs (saRNAs) are short double-stranded oligonucleotides that selectively increase gene transcription. Here, we describe the development of an saRNA that upregulates the transcription factor CCATT/enhancer binding protein alpha (CEBPA), investigate its mode of action, and describe its development into a clinical candidate. A bioinformatically directed nucleotide walk around the CEBPA gene identified an saRNA sequence that upregulates CEBPA mRNA 2.5-fold in human hepatocellular carcinoma cells...
August 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28882222/role-of-the-trna-derived-small-rnas-in-cancer-new-potential-biomarkers-and-target-for-therapy
#7
Veronica Balatti, Yuri Pekarsky, Carlo M Croce
Noncoding RNAs are untranslated RNA molecules that can be divided into two main types: infrastructural, including transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), and regulatory, including long ncRNAs (lncRNAs) and small ncRNAs (sRNA). Among small ncRNA, the role of microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) in cancer is well documented. Recently, other small ncRNAs have been described. In particular, tRNA-derived small RNAs (tsRNA) have been found to be frequently dysregulated in cancer. Since tsRNAs can be considered unique sequences and are able to bind both Argonaute proteins (like miRNAs) and Piwi proteins (like piRNAs), their dysregulation could play a critical role in cancer by interfering with gene expression regulation at different levels...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/28876208/deep-sequencing-uncovers-rice-long-sirnas-and-its-involvement-in-immunity-against-rhizoctonia-solani
#8
Dongdong Niu, Xin Zhang, Xiaoou Song, Zhihui Wang, Yanqiang Li, Lulu Qiao, Zhaoyun Wang, Junzhong Liu, Yiwen Deng, Zuhua He, Donglei Yang, Renyi Liu, Yangli Wang, Hongwei Zhao
Small RNA (sRNA) is a class of non-coding RNA that can silence the expression of target genes. In rice, the majority of characterized sRNAs are within the range of 21 to 24 nucleotide long, whose biogenesis and function are associated with a specific sets of components, such as Dicer-like (OsDCLs) and Argonaute proteins (OsAGOs). Rice sRNAs longer than 24 nt are occasionally reported, with biogenesis and functional mechanism uninvestigated, especially in a context of defense responses against pathogen infection...
September 6, 2017: Phytopathology
https://www.readbyqxmd.com/read/28875539/ago18b-negatively-regulates-determinacy-of-spikelet-meristems-on-the-tassel-central-spike-in-maize
#9
Wei Sun, Xiaoli Xiang, Lihong Zhai, Dan Zhang, Zheng Cao, Lei Liu, Zuxin Zhang
The maize tassel represents an indeterminate male inflorescence. The number of primordia that a given inflorescence meristem produces is related to its determinacy, i.e., capacity for continued meristem activity. Transcription factors (TFs) controlling determinacy in tassel axillary meristems are well studied in maize, and small RNAs are known to influence tassel development by repressing targets including tassel-related TFs. As core components of the RNA-inducible silence complex (RISC), Argonaute (AGO) proteins are required for small RNA-mediated repression...
September 6, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28871632/specific-direct-amplified-microrna-detection-with-microrna-argonaute-2-cleavage-miracle-beacons
#10
Benjamin Luby, Gang Zheng
MicroRNA detection is a valuable method for determining cell identity. Molecular beacons are elegant sensors that can transform intracellular microRNA concentration into a fluorescence intensity. While target binding enhances beacon fluorescence, the degree of enhancement is insufficient for demanding applications. Addition of specialty nucleases can allow target recycling and amplify the signal, but this process complicates the assay. We develop and characterize a novel class of beacons susceptible to the endogenous nuclease Argonaute-2 (Ago2)...
September 4, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28866430/the-role-of-microrna-molecules-and-microrna-regulating-machinery-in-the-pathogenesis-and-progression-of-epithelial-ovarian-cancer
#11
REVIEW
Xiyin Wang, Mircea Ivan, Shannon M Hawkins
MicroRNA molecules are small, single-stranded RNA molecules that function to regulate networks of genes. They play important roles in normal female reproductive tract biology, as well as in the pathogenesis and progression of epithelial ovarian cancer. DROSHA, DICER, and Argonaute proteins are components of the microRNA-regulatory machinery and mediate microRNA production and function. This review discusses aberrant expression of microRNA molecules and microRNA-regulating machinery associated with clinical features of epithelial ovarian cancer...
August 30, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28854734/amide-linkages-mimic-phosphates-in-rna-interactions-with-proteins-and-are-well-tolerated-in-the-guide-strand-of-short-interfering-rnas
#12
Daniel Mutisya, Travis Hardcastle, Samwel K Cheruiyot, Pradeep S Pallan, Scott D Kennedy, Martin Egli, Melissa L Kelley, Anja van Brabant Smith, Eriks Rozners
While the use of RNA interference (RNAi) in molecular biology and functional genomics is a well-established technology, in vivo applications of synthetic short interfering RNAs (siRNAs) require chemical modifications. We recently found that amides as non-ionic replacements for phosphodiesters may be useful modifications for optimization of siRNAs. Herein, we report a comprehensive study of systematic replacement of a single phosphate with an amide linkage throughout the guide strand of siRNAs. The results show that amides are surprisingly well tolerated in the seed and central regions of the guide strand and increase the silencing activity when placed between nucleosides 10 and 12, at the catalytic site of Argonaute...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28838355/sixteen-years-of-meiotic-silencing-by-unpaired-dna
#13
T M Hammond
The filamentous fungus Neurospora crassa possesses a process called meiotic silencing by unpaired DNA (MSUD). MSUD has a remarkable ability to scan homologous chromosomes for unpaired DNA during meiosis. After unpaired DNA is identified, MSUD silences all RNA from the unpaired DNA along with any RNA transcribed from homologous sequences at other locations in the genome, regardless of their pairing state. The mechanism by which unpaired DNA is detected is unknown. Unpaired DNA segments can be as short as 1.3kb, if not shorter, and DNA sequences with only a small level of polymorphism (6%) can be considered unpaired by MSUD...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/28837617/structural-characterisation-of-tnrc6a-nuclear-localisation-signal-in-complex-with-importin-alpha
#14
Jessica J Chaston, Alastair Gordon Stewart, Mary Christie
The GW182/TNRC6 family of proteins are central scaffolds that link microRNA-associated Argonaute proteins to the cytoplasmic decay machinery for targeted mRNA degradation processes. Although nuclear roles for the GW182/TNRC6 proteins are unknown, recent reports have demonstrated nucleocytoplasmic shuttling activity that utilises the importin-α and importin-β transport receptors for nuclear translocation. Here we describe the structure of mouse importin-α in complex with the TNRC6A nuclear localisation signal peptide...
2017: PloS One
https://www.readbyqxmd.com/read/28835645/the-evolution-of-animal-argonautes-evidence-for-the-absence-of-antiviral-ago-argonautes-in-vertebrates
#15
Niels Wynant, Dulce Santos, Jozef Vanden Broeck
In addition to mediating regulation of endogenous gene expression, RNA interference (RNAi) in plants and invertebrates plays a crucial role in defense against viruses via virus-specific siRNAs. Different studies have demonstrated that the functional diversity of RNAi in animals is linked to the diversification of the Argonaute superfamily, central components of RISCs (RNA induced silencing complexes). The animal Argonaute superfamily is traditionally grouped into AGO and PIWI Argonautes. Yet, by performing phylogenetic analyses and determining the selective evolutionary pressure in the metazoan Argonaute superfamily, we provide evidence for the existence of three conserved Argonaute lineages between basal metazoans and protostomes, namely siRNA-class AGO, miRNA-class AGO and PIWI Argonautes...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835265/conservation-and-divergence-of-small-rna-pathways-and-micrornas-in-land-plants
#16
Chenjiang You, Jie Cui, Hui Wang, Xinping Qi, Li-Yaung Kuo, Hong Ma, Lei Gao, Beixin Mo, Xuemei Chen
BACKGROUND: As key regulators of gene expression in eukaryotes, small RNAs have been characterized in many seed plants, and pathways for their biogenesis, degradation, and action have been defined in model angiosperms. However, both small RNAs themselves and small RNA pathways are not well characterized in other land plants such as lycophytes and ferns, preventing a comprehensive evolutionary perspective on small RNAs in land plants. RESULTS: Using 25 representatives from major lineages of lycophytes and ferns, most of which lack sequenced genomes, we characterized small RNAs and small RNA pathways in these plants...
August 23, 2017: Genome Biology
https://www.readbyqxmd.com/read/28831191/red-blood-cells-release-microparticles-containing-human-argonaute-2-and-mirnas-to-target-genes-of-plasmodium-falciparum
#17
Zhensheng Wang, Juemin Xi, Xiao Hao, Weiwei Deng, Juan Liu, Chunyan Wei, Yuhui Gao, Lianhui Zhang, Heng Wang
Red blood cells (RBCs) are known to function as a refuge for providing food resources and as a shelter against the host's immune system after malaria parasite (Plasmodium) infection. Recent studies have reported significant production of extracellular vesicles (microparticles, MPs) in the circulation of malaria patients. However, it is unclear how these extracellular vesicles are generated and what their biological functions are. In this study, we isolated the MPs from a culture medium of normal RBCs and malaria parasite-infected RBCs (iRBCs), compared their quantity and origins, and profiled their miRNAs by deep sequencing...
August 23, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28827780/rna-interference-in-the-asian-longhorned-beetle-identification-of-key-rnai-genes-and-reference-genes-for-rt-qpcr
#18
Thais B Rodrigues, Ramesh Kumar Dhandapani, Jian J Duan, Subba Reddy Palli
Asian Longhorned Beetle (ALB) Anoplophora glabripennis is a serious invasive forest pest in several countries including the United States, Canada, and Europe. RNA interference (RNAi) technology is being developed as a novel method for pest management. Here, we identified the ALB core RNAi genes including those coding for Dicer, Argonaute, and double-stranded RNA-binding proteins (dsRBP) as well as for proteins involved in dsRNA transport and the systemic RNAi. We also compared expression of six potential reference genes that could be used to normalize gene expression and selected gapdh and rpl32 as the most reliable genes among different tissues and stages of ALB...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827574/mirna-584-3p-inhibits-gastric-cancer-progression-by-repressing-yin-yang-1-facilitated-mmp-14-expression
#19
Liduan Zheng, Yajun Chen, Lin Ye, Wanju Jiao, Huajie Song, Hong Mei, Dan Li, Feng Yang, Huanhuan Li, Kai Huang, Qiangsong Tong
Recent evidence shows the emerging roles of promoter-targeting endogenous microRNAs (miRNAs) in regulating gene transcription. However, miRNAs affecting the transcription of matrix metalloproteinase 14 (MMP-14) in gastric cancer remain unknown. Herein, through integrative mining of public datasets, we identified the adjacent targeting sites of Yin Yang 1 (YY1) and miRNA-584-3p (miR-584-3p) within MMP-14 promoter. We demonstrated that YY1 directly targeted the MMP-14 promoter to facilitate its expression in gastric cancer cells...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819099/the-genetic-basis-of-natural-variation-in-a-phoretic-behavior
#20
Daehan Lee, Heeseung Yang, Jun Kim, Shannon Brady, Stefan Zdraljevic, Mostafa Zamanian, Heekyeong Kim, Young-Ki Paik, Leonid Kruglyak, Erik C Andersen, Junho Lee
Phoresy is a widespread form of commensalism that facilitates dispersal of one species through an association with a more mobile second species. Dauer larvae of the nematode Caenorhabditis elegans exhibit a phoretic behavior called nictation, which could enable interactions with animals such as isopods or snails. Here, we show that natural C. elegans isolates differ in nictation. We use quantitative behavioral assays and linkage mapping to identify a genetic locus (nict-1) that mediates the phoretic interaction with terrestrial isopods...
August 17, 2017: Nature Communications
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