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https://www.readbyqxmd.com/read/29150439/suppression-of-fip200-and-autophagy-by-tumor-derived-lactate-promotes-na%C3%A3-ve-t-cell-apoptosis-and-affects-tumor-immunity
#1
Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity...
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29133395/rna-stem-structure-governs-coupling-of-dicing-and-gene-silencing-in-rna-interference
#2
Hye Ran Koh, Amirhossein Ghanbariniaki, Sua Myong
PremicroRNAs (premiRNAs) possess secondary structures consisting of a loop and a stem with multiple mismatches. Despite the well-characterized RNAi pathway, how the structural features of premiRNA contribute to dicing and subsequent gene-silencing efficiency remains unclear. Using single-molecule FISH, we demonstrate that cytoplasmic mRNA, but not nuclear mRNA, is reduced during RNAi. The dicing rate and silencing efficiency both increase in a correlated manner as a function of the loop length. In contrast, mismatches in the stem drastically diminish the silencing efficiency without impacting the dicing rate...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29126849/introduction-of-2-o-benzyl-abasic-nucleosides-to-the-3-overhang-regions-of-sirnas-greatly-improves-nuclease-resistance
#3
Yuki Nagaya, Yoshiaki Kitamura, Aya Shibata, Masato Ikeda, Yukihiro Akao, Yukio Kitade
Chemically modified siRNAs containing 2-O-benzyl-1-deoxy-d-ribofuranose (R(H)OBn) in their 3'-overhang region were significantly more resistant towards serum nucleases than siRNAs possessing the natural nucleoside in this region. The knockdown efficacies and binding affinities of these modified siRNAs to the recombinant human Argonaute protein 2 (hAgo2) PAZ domain were comparable with that of siRNA with a thymidine dimer at the 3'-end.
October 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29120412/bortezomib-induced-mirnas-direct-epigenetic-silencing-of-locus-genes-and-trigger-apoptosis-in-leukemia
#4
Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu, Lu-Hao Wang, Ju-Ming Wang
MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29117550/microrna-regulation-of-nachr-expression-and-nicotine-dependent-behavior-in-c-%C3%A2-elegans
#5
Manish Rauthan, Jianke Gong, Jinzhi Liu, Zhaoyu Li, Seth A Wescott, Jianfeng Liu, X Z Shawn Xu
Chronic exposure to nicotine upregulates nicotinic acetylcholine receptors (nAChRs), and such upregulation is critical for the development of nicotine dependence in humans and animal models. However, how nicotine upregulates nAChRs is not well understood. Here, we identify a key role for microRNA in regulating nicotine-dependent behavior by modulating nAChR expression in C. elegans. We show that the nAChR gene acr-19 and alg-1, a key Argonaute-family member in the microRNA machinery, are specifically required for nicotine withdrawal response following chronic nicotine treatment...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29116117/circulating-microrna-92b-3p-as-a-novel-biomarker-for-monitoring-of-synovial-sarcoma
#6
Koji Uotani, Tomohiro Fujiwara, Aki Yoshida, Shintaro Iwata, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Toshiyuki Kunisada, Ken Takeda, Joe Hasei, Kunihiko Numoto, Yutaka Nezu, Tsukasa Yonemoto, Takeshi Ishii, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki
The lack of useful biomarkers is a crucial problem for patients with soft tissue sarcomas (STSs). Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel impact as biomarkers for patients with malignant diseases, but their significance in synovial sarcoma (SS) patients remains unknown. Initial global miRNA screening using SS patient serum and SS cell culture media identified a signature of four upregulated miRNAs. Among these candidates, miR-92b-3p secretion from SS cells was confirmed, which was embedded within tumour-derived exosomes rather than argonaute-2...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29114017/a-microrna-feedback-loop-regulates-global-microrna-abundance-during-aging
#7
Sachi Inukai, Zachary Pincus, Alexandre de Lencastre, Frank J Slack
Expression levels of many microRNAs (miRNAs) change during aging, notably declining globally in a number of organisms and tissues across taxa. However, little is known about the mechanisms or the biological relevance for this change. We investigated the network of genes that controls miRNA transcription and processing during C. elegans aging. We found that miRNA biogenesis genes are highly networked with transcription factors and aging-associated miRNAs. In particular, miR-71, known to influence lifespan and itself upregulated during aging, represses alg-1/Argonaute expression post-transcriptionally during aging...
November 7, 2017: RNA
https://www.readbyqxmd.com/read/29107107/roles-of-trna-derived-fragments-in-human-cancers
#8
Chunxiao Sun, Ziyi Fu, Siwei Wang, Jun Li, Yongfei Li, Yanhong Zhang, Fan Yang, Jiahui Chu, Hao Wu, Xiang Huang, Wei Li, Yongmei Yin
Transfer RNAs (tRNAs) were traditionally considered to participate in protein translation. Recent studies have identified a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of pre- and mature tRNAs, which have been named tRNA-derived fragments. tRNA-derived fragments are classified into diverse subtypes based on the different cleavage positions of the pre- and mature tRNAs. Recently, accumulated evidence has shown that these tRNA-derived fragments are frequently dysregulated in several cancers...
October 26, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29104238/which-plant-proteins-are-involved-in-antiviral-defense-review-on-in-vivo-and-in-vitro-activities-of-selected-plant-proteins-against-viruses
#9
REVIEW
Oskar Musidlak, Robert Nawrot, Anna Goździcka-Józefiak
Plants have evolved a variety of defense mechanisms to tackle virus attack. Endogenous plant proteins can function as virus suppressors. Different types of proteins mediate defense responses against plant viruses. Pathogenesis-related (PR) proteins are activated upon pathogen infections or in different stress situations and their production is one of many components in plant defense. Ribosome-inactivating proteins (RIPs) suppress translation by enzymatically damaging ribosomes and they have been found to have antiviral activity...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29084265/mirna-independent-hepacivirus-variants-suggest-a-strong-evolutionary-pressure-to-maintain-mir-122-dependence
#10
Yingpu Yu, Troels K H Scheel, Joseph M Luna, Hachung Chung, Eiko Nishiuchi, Margaret A Scull, Natalia Echeverría, Inna Ricardo-Lax, Amit Kapoor, Ian W Lipkin, Thomas J Divers, Douglas F Antczak, Bud C Tennant, Charles M Rice
Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5'UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5' end of NPHV replacing orthologous HCV sequences...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29079435/molecular-dynamics-and-binding-selectivity-of-nucleotides-and-polynucleotide-substrates-with-eif2c2-ago2-paz-domain
#11
Mahmoud Kandeel, Yukio Kitade
RNA interference (RNAi) constitutes a major target in drug discovery. Recently, we reported that the Argonaute protein 2 (Ago2) PAZ domain selectively binds with all ribonucleotides except adenine and poorly recognizes deoxyribonucleotides. The binding properties of the PAZ domain with polynucleotides and the molecular mechanisms of substrates' selectivity remains unclear. In this study, the binding potencies of polynucleotides and the associated conformational and dynamic changes in PAZ domain are investigated...
October 25, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29040713/human-argonaute3-has-slicer-activity
#12
Mi Seul Park, Hong-Duc Phan, Florian Busch, Samantha H Hinckley, James A Brackbill, Vicki H Wysocki, Kotaro Nakanishi
Of the four human Argonaute (AGO) paralogs, only AGO2 has been shown to have slicer activity. The others (AGO1, AGO3 and AGO4) have been thought to assemble with microRNAs to form slicer-independent effector complexes that bind target mRNAs and silence gene expression through translational repression and deadenylation but not cleavage. Here, we report that recombinant AGO3 loaded with miR-20a cleaves complementary target RNAs, whereas AGO3 loaded with let-7a, miR-19b or miR-16 does not, indicating that AGO3 has slicer activity but that this activity depends on the guide RNA...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040304/characterization-of-the-zika-virus-induced-small-rna-response-in-aedes-aegypti-cells
#13
Margus Varjak, Claire L Donald, Timothy J Mottram, Vattipally B Sreenu, Andres Merits, Kevin Maringer, Esther Schnettler, Alain Kohl
RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25-29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29036592/gain-and-loss-of-small-rna-classes-characterization-of-small-rnas-in-the-parasitic-nematode-family-strongyloididae
#14
Anja Holz, Adrian Streit
The nematode family Strongyloididae is of particular interest because it contains important parasites of medical and veterinary relevance. In addition, species of this family can form parasitic and free-living generations and it also occupies an interesting phylogenetic position within the nematodes. Nematodes differ in several ways from other taxa with respect to their small non-coding RNAs. Recent comparative studies revealed that there is also considerable variability within the nematodes. However, no Strongyloididae species or close relative was included in these studies...
September 25, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29031931/global-analysis-of-ago2-bound-rnas-reveals-that-mirnas-induce-cleavage-of-target-rnas-with-limited-complementarity
#15
Eunsun Jung, Youngmo Seong, Bohyun Jeon, Hoseok Song, Young-Soo Kwon
Among the four Argonaute family members in mammals, only AGO2 protein retains endonuclease activity and facilitates cleavage of target RNAs base-pairing with highly complementary guide RNAs. Despite the deeply conserved catalytic activity, only a small number of targets have been reported to extensively base pair with cognate miRNAs to be cleaved by AGO2. Here, we analyzed AGO2-bound RNAs by CrossLinking ImmunoPrecipitation (CLIP) of genetically modified cells that express epitope-tagged AGO2 from the native genomic locus...
November 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29030851/cellular-approaches-in-investigating-argonaute2-dependent-rna-silencing
#16
Cai Zhang, Joonbae Seo, Takahisa Nakamura
In mammals, there are four Argonaute (Ago) family proteins that play crucial roles in RNA silencing, a process wherein microRNA (miRNA) mediates inhibition of target mRNA translation. Among the Ago proteins, Argonaute2 (Ago2) uniquely possesses an endoribonuclease (slicer) activity that is critical for the biogenesis of specific miRNAs and mRNA cleavage. This Ago2 slicer activity is required for postnatal development. Despite its important roles, there are still gaps in our understanding of the mechanistic basis of Ago2's unique functions in vivo due to a limited availability of experimental tools...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030849/assessing-mir-451-activity-and-its-role-in-erythropoiesis
#17
Dmitry A Kretov, Andrew M Shafik, Daniel Cifuentes
The ability to microinject small RNAs and mRNAs into zebrafish embryos, of different genetic backgrounds, allows for the precise dissection of microRNA processing pathways at the molecular level, while simultaneously provides insight into their physiologic role. Here, we apply such an approach to determine the impact of Argonaute 2 in the processing of miR-451, a vertebrate-specific microRNA required for terminal erythrocyte differentiation. This was achieved using fluorescent microRNA reporter sensor assays and phenotype rescue experiments...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030845/nucleic-acid-binding-assay-of-argonaute-protein-using-fluorescence-polarization
#18
Tomohiro Miyoshi
Nucleic acid binding by the Argonaute protein is an important trigger step in the Argonaute-dependent gene silencing system. We established an in vitro method to detect the nucleic acid binding activity of the Argonaute protein by fluorescence polarization. In this chapter, we will describe the expression and purification of the prokaryotic (Rhodobacter sphaeroides) Argonaute protein, and the nucleic acid-binding analysis using a Fluorescence Polarization System (Beacon 2000).
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030844/kinetic-analysis-of-small-silencing-rna-production-by%C3%A2-human-and-drosophila-dicer-enzymes-in-vitro
#19
Susan E Liao, Ryuya Fukunaga
Dicer enzymes produce small silencing RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), which then are loaded into Argonaute proteins and act as sequence-specific guides. A powerful tool to understand the molecular mechanism of small silencing RNA production by Dicers is an in vitro RNA processing assay using recombinant Dicer proteins. Such biochemical analyses have elucidated the substrate specificities and kinetics of Dicers, the mechanism by which the length of small RNAs produced by Dicers is determined, and the effects of Dicer-partner proteins and endogenous small molecules such as ATP and inorganic phosphate on small RNA production by Dicers, among others...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030843/cclip-seq-retrieval-of-chimeric-reads-from-hits-clip-clip-seq-libraries
#20
Panagiotis Alexiou, Manolis Maragkakis, Zissimos Mourelatos, Anastassios Vourekas
HITS-CLIP (High-Throughput Sequencing after in vivo Crosslinking and Immunoprecipitation, CLIP-Seq) libraries contain fragments of the RNA sequences bound in vivo by an RNA binding protein (RBP). Such fragments, especially if they represent RNA duplexes bound in vivo by the RBP, can occasionally be ligated together to form chimeric CLIP tags. Chimeric CLIP tags from Argonaute CLIP libraries can provide the exact base pairing profiles of small RNAs with their target RNA sequences, thus solving a critical problem in the field of post-transcriptional regulation...
2018: Methods in Molecular Biology
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