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https://www.readbyqxmd.com/read/28339467/a-non-canonical-rna-degradation-pathway-suppresses-rnai-dependent-epimutations-in-the-human-fungal-pathogen-mucor-circinelloides
#1
Silvia Calo, Francisco E Nicolás, Soo Chan Lee, Ana Vila, Maria Cervantes, Santiago Torres-Martinez, Rosa M Ruiz-Vazquez, Maria E Cardenas, Joseph Heitman
Mucorales are a group of basal fungi that includes the casual agents of the human emerging disease mucormycosis. Recent studies revealed that these pathogens activate an RNAi-based pathway to rapidly generate drug-resistant epimutant strains when exposed to stressful compounds such as the antifungal drug FK506. To elucidate the molecular mechanism of this epimutation pathway, we performed a genetic analysis in Mucor circinelloides that revealed an inhibitory role for the non-canonical RdRP-dependent Dicer-independent silencing pathway, which is an RNAi-based mechanism involved in mRNA degradation that was recently identified...
March 24, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28335016/trna-derived-small-rnas-target-transposable-element-transcripts
#2
German Martinez, Sarah G Choudury, R Keith Slotkin
tRNA-derived RNA fragments (tRFs) are 18-26 nucleotide small RNAs that are not random degradation products, but are rather specifically cleaved from mature tRNA transcripts. Abundant in stressed or viral-infected cells, the function and potential targets of tRFs are not known. We identified that in the unstressed wild-type male gamete containing pollen of flowering plants, and analogous reproductive structure in non-flowering plant species, tRFs accumulate to high levels. In the reference plant Arabidopsis thaliana, tRFs are processed by Dicer-like 1 and incorporated into Argonaute1 (AGO1), akin to a microRNA...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28331089/diversity-distribution-and-evolution-of-tomato-viruses-in-china-uncovered-by-small-rna-sequencing
#3
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/28330621/synergic-functions-of-mirnas-determine-neuronal-fate-of-adult-neural-stem-cells
#4
Meritxell Pons-Espinal, Emanuela de Luca, Matteo Jacopo Marzi, Ruth Beckervordersandforth, Andrea Armirotti, Francesco Nicassio, Klaus Fabel, Gerd Kempermann, Davide De Pietri Tonelli
Adult neurogenesis requires the precise control of neuronal versus astrocyte lineage determination in neural stem cells. While microRNAs (miRNAs) are critically involved in this step during development, their actions in adult hippocampal neural stem cells (aNSCs) has been unclear. As entry point to address that question we chose DICER, an endoribonuclease essential for miRNA biogenesis and other RNAi-related processes. By specific ablation of Dicer in aNSCs in vivo and in vitro, we demonstrate that miRNAs are required for the generation of new neurons, but not astrocytes, in the adult murine hippocampus...
March 10, 2017: Stem Cell Reports
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
#5
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...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325765/caenorhabditis-elegans-rig-i-homolog-mediates-antiviral-rna-interference-downstream-of-dicer-dependent-biogenesis-of-viral-small-interfering-rnas
#6
Stephanie R Coffman, Jinfeng Lu, Xunyang Guo, Jing Zhong, Hongshan Jiang, Gina Broitman-Maduro, Wan-Xiang Li, Rui Lu, Morris Maduro, Shou-Wei Ding
Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28325284/type-i-interferons-impede-short-hairpin-rna-mediated-rnai-via-inhibition-of-dicer-mediated-processing-to-small-interfering-rna
#7
Mitsuhiro Machitani, Fuminori Sakurai, Keisaku Wakabayashi, Kosuke Takayama, Masashi Tachibana, Hiroyuki Mizuguchi
RNAi by short hairpin RNA (shRNA) is a powerful tool not only for studying gene functions in various organisms, including mammals, but also for the treatment of severe disorders. However, shRNA-expressing vectors can induce type I interferon (IFN) expression by activation of innate immune responses, leading to off-target effects and unexpected side effects. Several strategies have been developed to prevent type I IFN induction. On the other hand, it has remained unclear whether type I IFNs have effects on shRNA-mediated RNAi...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28319645/the-atypical-genesis-and-bioavailability-of-the-plant-based-small-rna-mir2911-bulking-up-while-breaking-down
#8
Jian Yang, Natee Kongchan, Cecilia Primo Planta, Joel R Neilson, Kendal D Hirschi
SCOPE: The uptake of dietary plant small RNAs (sRNAs) in consumers remains controversial, which is mainly due to low dietary content in combination with poor fractional absorption. MIR2911, among all the plant sRNAs including microRNAs, has been shown to be one of the most robustly absorbed sRNAs. Here we analyze the unusual abundance and unique genesis of MIR2911 during vegetable processing. METHODS AND RESULTS: Using qRT-PCR, the abundance of MIR2911 increased dramatically in macerated tissues while other microRNAs degraded...
March 20, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28319071/xrn2-promotes-emt-and-metastasis-through-regulating-maturation-of-mir-10a
#9
H Zhang, Y Lu, E Chen, X Li, B Lv, H G Vikis, P Liu
MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317870/structural-and-functional-studies-of-a-noncanonical-dicer-from-entamoeba-histolytica
#10
Xiang Yu, Xuhang Li, Lina Zheng, Jinbiao Ma, Jianhua Gan
RNaseIII proteins are dsRNA-specific endonucleases involved in many important biological processes, such as small RNA processing and maturation in eukaryotes. Various small RNAs have been identified in a protozoan parasite Entamoeba histolytica. EhRNaseIII is the only RNaseIII endonuclease domain (RIIID)-containing protein in E. histolytica. Here, we present three crystal structures that reveal several unique structural features of EhRNaseIII, especially the interactions between the two helixes (α1 and α7) flanking the RIIID core domain...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289490/cooperative-processing-of-primary-mirnas-by-dus16-and-dcl3-in-the-unicellular-green-alga-chlamydomonas-reinhardtii
#11
Tomohito Yamasaki, Heriberto Cerutti
We have previously reported that the RNA-binding protein Dull slicer 16 (DUS16) plays a key role in the processing of primary miRNAs (pri-miRNAs) in the unicellular green alga Chlamydomonas reinhardtii. In the present report, we elaborate on the interaction of DUS16 with Dicer-like 3 (DCL3) during pri-miRNA processing. Comprehensive analyses of small RNA libraries derived from mutant and wild-type algal strains allowed the de novo prediction of 35 pri-miRNA genes, including 9 previously unknown ones. The pri-miRNAs dependent on DUS16 for processing largely overlapped with those dependent on DCL3...
2017: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/28287718/regulating-mirna-21-biogenesis-by-bi-functional-small-molecules
#12
Hao Yan, Umesh Bhattarai, Zhi-Fo Guo, Fu-Sen Liang
MicroRNAs (miRNAs) are non-coding RNAs that regulate translation by targeting mRNAs. In their biogenesis, precursor miRNAs (pre-miRNAs) are cleaved by RNase Dicer to give mature miRNAs. Herein, we report a new strategy to regulate miRNA biogenesis by using bi-functional small molecules that block Dicer catalyzed pre-miRNA cleavage. The bi-functional molecules consist of a pre-miRNA binding unit connected by a linker to a Dicer inhibiting unit. Recognition of a target pre-miRNA by the RNA binding unit brings the Dicer inhibitor unit into close proximity to the pre-miRNA cleavage site where it inhibits Dicer...
March 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28287396/topical-treatment-of-herpes-simplex-virus-infection-with-enzymatically-created-sirna-swarm
#13
Henrik Paavilainen, Jenni Lehtinen, Alesia Romanovskaya, Michaela Nygårdas, Dennis H Bamford, Minna M Poranen, Veijo Hukkanen
BACKGROUND: Herpes simplex virus (HSV) is a common human pathogen. Despite current antivirals, it causes a significant medical burden. Drug resistant strains exist and they are especially prevalent in immunocompromised patients and in HSV eye infections. New treatment modalities are needed. METHODS: BALB/c mice were corneally infected with HSV and subsequently treated with a swarm of enzymatically created, Dicer-substrate small interfering RNA (siRNA) molecules that targeted the HSV gene UL29...
March 13, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28283070/circular-concatemers-of-ultra-short-dna-segments-produce-regulatory-rnas
#14
Sarah E Allen, Iris Hug, Sylwia Pabian, Iwona Rzeszutek, Cristina Hoehener, Mariusz Nowacki
In the ciliated protozoan Paramecium tetraurelia, Piwi-associated small RNAs are generated upon the elimination of tens of thousands of short transposon-derived DNA segments as part of development. These RNAs then target complementary DNA for elimination in a positive feedback process, contributing to germline defense and genome stability. In this work, we investigate the formation of these RNAs, which we show to be transcribed directly from the short (length mode 27 bp) excised DNA segments. Our data support a mechanism whereby the concatenation and circularization of excised DNA segments provides a template for RNA production...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28267232/dcl2-rdr6-dependent-transitive-silencing-of-smxl4-and-smxl5-in-arabidopsis-dcl4-mutants-causes-phloem-transport-defect-and-carbohydrate-over-accumulation
#15
Yu-Yi Wu, Bo-Han Hou, Wen-Chi Lee, Shin-Hua Lu, Chen-Jui Yang, Hervé Vaucheret, Ho-Ming Chen
DICER-LIKE (DCL) enzymes process double-stranded RNA into small RNAs that act as regulators of gene expression. Arabidopsis DCL4 and DCL2 each allow post-transcriptional gene silencing (PTGS) of viruses and transgenes, but primary PTGS-prone DCL4 outcompetes transitive PTGS-prone DCL2 in wild-type plants. This hierarchy likely prevents DCL2 to have detrimental effects on endogenous genes. Indeed, dcl4 mutants exhibit developmental defects and increased sensitivity to genotoxic stress. In this study, the mechanism underlying dcl4 defects was investigated using genetic, biochemical and high-throughput sequencing approaches...
March 7, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28266707/the-agotrons-gene-regulators-or-argonaute-protectors
#16
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/28262484/the-antiviral-rna-interference-response-provides-resistance-to-lethal-arbovirus-infection-and-vertical-transmission-in-caenorhabditis-elegans
#17
Don B Gammon, Takao Ishidate, Lichao Li, Weifeng Gu, Neal Silverman, Craig C Mello
The recent discovery of the positive-sense single-stranded RNA (ssRNA) Orsay virus (OV) as a natural pathogen of the nematode Caenorhabditis elegans has stimulated interest in exploring virus-nematode interactions. However, OV infection is restricted to a small number of intestinal cells, even in nematodes defective in their antiviral RNA interference (RNAi) response, and is neither lethal nor vertically transmitted. Using a fluorescent reporter strain of the negative-sense ssRNA vesicular stomatitis virus (VSV), we show that microinjection of VSV particles leads to a dose-dependent, muscle tissue-tropic, lethal infection in C...
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28256530/translational-repression-by-a-miniature-inverted-repeat-transposable-element-in-the-3-untranslated-region
#18
Jianqiang Shen, Juhong Liu, Kabin Xie, Feng Xing, Fang Xiong, Jinghua Xiao, Xianghua Li, Lizhong Xiong
Transposable elements constitute a substantial portion of eukaryotic genomes and contribute to genomic variation, function, and evolution. Miniature inverted-repeat transposable elements (MITEs), as DNA transposons, are widely distributed in plant and animal genomes. Previous studies have suggested that retrotransposons act as translational regulators; however, it remains unknown how host mRNAs are influenced by DNA transposons. Here we report a translational repression mechanism mediated by a stowaway-like MITE (sMITE) embedded in the 3'-untranslated region (3'-UTR) of Ghd2, a member of the CCT (CONSTANS [CO], CO-LIKE and TIMING OF CAB1) gene family in rice...
March 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28240549/small-molecule-inhibition-of-microrna-210-reprograms-an-oncogenic-hypoxic-circuit
#19
Matthew G Costales, Christopher L Haga, Sai Pradeep Velagapudi, Jessica L Childs-Disney, Donald G Phinney, Matthew D Disney
A hypoxic state is critical to the metastatic and invasive characteristics of cancer. Numerous pathways play critical roles in cancer maintenance, many of which include noncoding RNAs such as microRNA (miR)-210 that regulates hypoxia inducible factors (HIFs). Herein, we describe the identification of a small molecule named Targapremir-210 that binds to the Dicer site of the miR-210 hairpin precursor. This interaction inhibits production of the mature miRNA, derepresses glycerol-3-phosphate dehydrogenase 1-like enzyme (GPD1L), a hypoxia-associated protein negatively regulated by miR-210, decreases HIF-1α, and triggers apoptosis of triple negative breast cancer cells only under hypoxic conditions...
February 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28240178/efficient-colonic-delivery-of-dsirna-by-pectin-coated-polyelectrolyte-complex-nanoparticles-preparation-characterization-and-improved-gastric-survivability
#20
Zahid Hussain, Haliza Katas, Set Li Yan, Diyanadalila Jamaludin
BACKGROUND: Despite having excellent anticancer efficacy and ability to knockdown gene expression, the therapeutic feasibility of Dicer-substrate small interference RNA (DsiRNA) is limited due to its poor cellular uptake, chemical instability and rapid degradation in biological environments. OBJECTIVE: The present study was aimed to circumvent the pharmaceutical issues related to DsiRNA delivery to colon for the treatment of colorectal cancer. METHOD: In this study, we have prepared water-soluble chitosan (WSC)-DsiRNA complex nanoparticles (NPs) by a simple complexation method and subsequently coated with pectin to protect DsiRNA from gastric milieu...
February 24, 2017: Current Drug Delivery
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