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https://www.readbyqxmd.com/read/29435938/transgene-like-animal-models-using-intronic-micrornas
#1
Shi-Lung Lin, Shin-Ju E Chang, Shao-Yao Ying
Transgenic animal models are valuable tools for testing gene functions and drug mechanisms in vivo. They are also the best similitude for a human body for etiological and pathological research of diseases. All pharmaceutically developed medicines must be proven to be safe and effective in animals before approval by the Food and Drug Administration (FDA) to be used in clinical trials. To this end, the transgenic animal models of diseases serve as the front line of drug evaluation. However, there is currently no transgenic animal model for microRNA (miRNA)-related research...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29428901/fragile-x-mental-retardation-protein-participates-in-non-coding-rna-pathways
#2
En-Hui Li, Xin Zhao, Ce Zhang, Wei Liu
Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells...
February 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29386086/up-regulation-of-mir-324-5p-inhibits-proliferation-and-invasion-of-colorectal-cancer-cells-by-targeting-elavl1
#3
Chijiang Gu, Mingyuan Zhang, Weiliang Sun, Changzheng Dong
Colorectal cancer (CRC) is a common clinical cancer, which remains incurable in most cases. MiRNAs are reported to playa part in development of various tumors. In the present study, we found that miR-324-5p was down-regulated in colorectal cancer cells while ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-Like Protein 1 (ELAVL1) showed a higher expression. MiR-324-5p transfection significantly inhibited the proliferation as well as invasion in both SW620 and SW480 cells. MiR-324-5p mimics transfection markedly decreased the expression of ELAVL1...
January 31, 2018: Oncology Research
https://www.readbyqxmd.com/read/29373753/dicer-partner-protein-tunes-the-length-of-mirnas-using-base-mismatch-in-the-pre-mirna-stem
#4
Li Zhu, Suresh K Kandasamy, Ryuya Fukunaga
Dicer partner proteins Drosophila Loquacious-PB (Loqs-PB) and human TRBP tune the length of miRNAs produced by Dicer from a subset of pre-miRNAs and thereby alter their target repertoire, by an unknown mechanism. Here, we developed a novel high-throughput method that we named Dram-seq (Dice randomized pre-miRNA pool and seq) to study length distributions of miRNAs produced from thousands of different pre-miRNA variants. Using Dram-seq, we found that a base-mismatch in the pre-miRNA stem can alter the length of miRNAs compared with a base-pair at the same position in both Drosophila and human, and is important for the miRNA length tuning by Loqs-PB...
January 24, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29361610/mir-9a-mediates-the-role-of-lethal-giant-larvae-as-an-epithelial-growth-inhibitor-in-drosophila
#5
Scott G Daniel, Atlantis D Russ, Kathryn M Guthridge, Ammad I Raina, Patricia S Estes, Linda M Parsons, Helena E Richardson, Joyce A Schroeder, Daniela C Zarnescu
Drosophila lethal giant larvae (lgl) encodes a conserved tumor suppressor with established roles in cell polarity, asymmetric division, and proliferation control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers, however, its mechanistic role as a tumor suppressor remains poorly understood. Based on a previously established connection between Lgl and Fragile X protein (FMRP), a miRNA associated translational regulator, we hypothesized that Lgl may exert its role as a tumor suppressor by interacting with the miRNA pathway...
December 20, 2017: Biology Open
https://www.readbyqxmd.com/read/29358748/stress-dependent-mir-980-regulation-of-rbfox1-a2bp1-promotes-ribonucleoprotein-granule-formation-and-cell-survival
#6
Mariya M Kucherenko, Halyna R Shcherbata
Upon stress, profound post-transcriptional adjustments of gene expression occur in spatially restricted, subcellular, membraneless compartments, or ribonucleoprotein (RNP) granules, which are formed by liquid phase separation of RNA-binding proteins with low complexity sequence domains (LCDs). Here, we show that Rbfox1 is an LCD-containing protein that aggregates into liquid droplets and amyloid-like fibers and promiscuously joins different nuclear and cytoplasmic RNP granules. Using Drosophila oogenesis as an in vivo system for stress response, we demonstrate a mechanism by which Rbfox1 promotes cell survival...
January 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29345184/temperature-dependent-small-rna-expression-in-drosophila-melanogaster
#7
Isabel Fast, David Rosenkranz
Temperature has a major impact on gene expression in ectotherms. But until recently, it was not clear in which way, if any, small non-coding RNAs such as miRNAs or piRNAs contribute to thermosensitive gene regulation. We have recently shown that temperature-responsive miRNAs in Drosophila drive adaptation to different ambient temperatures on the transcriptome level. Moreover, we demonstrated that higher temperatures lead to a more efficient piRNA-dependent transposon silencing, possibly due to heat-induced unfolding of RNA secondary structures...
January 18, 2018: RNA Biology
https://www.readbyqxmd.com/read/29338692/emerging-roles-for-microrna-in-the-regulation-of-drosophila-circadian-clock
#8
REVIEW
Yongbo Xue, Yong Zhang
BACKGROUND: The circadian clock, which operates within an approximately 24-h period, is closely linked to the survival and fitness of almost all living organisms. The circadian clock is generated through a negative transcription-translation feedback loop. microRNAs (miRNAs) are small non-coding RNAs comprised of approximately 22 nucleotides that post-transcriptionally regulate target mRNA by either inducing mRNA degradation or inhibiting translation. RESULTS: In recent years, miRNAs have been found to play important roles in the regulation of the circadian clock, especially in Drosophila...
January 16, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29314553/identification-of-mir-305-a-microrna-that-promotes-aging-and-its-target-mrnas-in-drosophila
#9
Makiko Ueda, Tetsuya Sato, Yasuyuki Ohkawa, Yoshihiro H Inoue
MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel Drosophila miRNAs involved in aging. We selected eight Drosophila miRNAs, displaying high homology with seed sequences of aging-related miRNAs characterized in other species, and investigated whether the over-expression of these miRNAs affected aging in Drosophila adult flies. The lifespan of adults over-expressing miR-305, a miRNA showing high homology with miR-239 in C. elegans, was significantly shorter...
January 5, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29312571/systematic-analysis-reveals-tumor-enhancing-and-suppressing-micrornas-in-drosophila-epithelial-tumors
#10
Zhiqiang Shu, Yi-Chun Huang, William H Palmer, Yoichiro Tamori, Gengqiang Xie, Hui Wang, Nan Liu, Wu-Min Deng
Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of Drosophila wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) lethal giant larvae (lgl), combined with overexpression of an active form of oncogene Ras (RasV12 ), and identified 51 mature miRNAs that changed significantly in tumorous discs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281264/piwi-interacting-rna-in-drosophila-biogenesis-transposon-regulation-and-beyond
#11
Haruna Yamashiro, Mikiko C Siomi
PIWI-interacting RNAs (piRNAs) are germline-enriched small RNAs that control transposons to maintain genome integrity. To achieve this, upon being processed from piRNA precursors, most of which are transcripts of intergenic piRNA clusters, piRNAs bind PIWI proteins, germline-specific Argonaute proteins, to form effector complexes. The mechanism of this piRNA-mediated transposon silencing pathway is fundamentally similar to that of siRNA/miRNA-dependent gene silencing in that a small RNA guides its partner Argonaute protein to target gene transcripts for repression via RNA-RNA base pairing...
December 27, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/29237851/micrornas-regulate-the-sesquiterpenoid-hormonal-pathway-in-drosophila-and-other-arthropods
#12
Zhe Qu, William G Bendena, Wenyan Nong, Kenneth W Siggens, Fernando G Noriega, Zhen-Peng Kai, Yang-Yang Zang, Alex C Koon, Ho Yin Edwin Chan, Ting Fung Chan, Ka Hou Chu, Hon Ming Lam, Michael Akam, Stephen S Tobe, Jerome Ho Lam Hui
Arthropods comprise the majority of all described animal species, and understanding their evolution is a central question in biology. Their developmental processes are under the precise control of distinct hormonal regulators, including the sesquiterpenoids juvenile hormone (JH) and methyl farnesoate. The control of the synthesis and mode of action of these hormones played important roles in the evolution of arthropods and their adaptation to diverse habitats. However, the precise roles of non-coding RNAs, such as microRNAs (miRNAs), controlling arthropod hormonal pathways are unknown...
December 20, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29233923/the-landscape-of-mirna-editing-in-animals-and-its-impact-on-mirna-biogenesis-and-targeting
#13
Lishi Li, Yulong Song, Xinrui Shi, Jianheng Liu, Shaolei Xiong, Wanying Chen, Qiang Fu, Zichao Huang, Nannan Gu, Rui Zhang
Adenosine-to-inosine (A-to-I) RNA editing regulates miRNA biogenesis and function. To date, fewer than 160 miRNA editing sites have been identified. Here, we present a quantitative atlas of miRNA A-to-I editing through the profiling of 201 pri-miRNA samples and 4694 mature miRNA samples in human, mouse, and Drosophila. We identified 4162 sites present in ∼80% of the pri-miRNAs and 574 sites in mature miRNAs. miRNA editing is prevalent in many tissue types in human. However, high-level editing is mostly found in neuronal tissues in mouse and Drosophila Interestingly, the edited miRNAs in neuronal and non-neuronal tissues in human gain two distinct sets of new targets, which are significantly associated with cognitive and organ developmental functions, respectively...
December 12, 2017: Genome Research
https://www.readbyqxmd.com/read/29233922/deep-experimental-profiling-of-microrna-diversity-deployment-and-evolution-across-the-drosophila-genus
#14
Jaaved Mohammed, Alex S Flynt, Alexandra M Panzarino, Md Mosharrof Hussein Mondal, Matthew DeCruz, Adam Siepel, Eric C Lai
To assess miRNA evolution across the Drosophila genus, we analyzed several billion small RNA reads across 12 fruit fly species. These data permit comprehensive curation of species- and clade-specific variation in miRNA identity, abundance, and processing. Among well-conserved miRNAs, we observed unexpected cases of clade-specific variation in 5' end precision, occasional antisense loci, and putatively noncanonical loci. We also used strict criteria to identify a large set (649) of novel, evolutionarily restricted miRNAs...
December 12, 2017: Genome Research
https://www.readbyqxmd.com/read/29198775/dynamic-mirna-mrna-regulations-are-essential-for-maintaining-drosophila-immune-homeostasis-during-micrococcus-luteus-infection
#15
Guanyun Wei, Lianjie Sun, Ruimin Li, Lei Li, Jiao Xu, Fei Ma
Pathogen bacteria infections can lead to dynamic changes of microRNA (miRNA) and mRNA expression profiles, which may control synergistically the outcome of immune responses. To reveal the role of dynamic miRNA-mRNA regulation in Drosophila innate immune responses, we have detailedly analyzed the paired miRNA and mRNA expression profiles at three time points during Drosophila adult males with Micrococcus luteus (M. luteus) infection using RNA- and small RNA-seq data. Our results demonstrate that differentially expressed miRNAs and mRNAs represent extensively dynamic changes over three time points during Drosophila with M...
November 30, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29196461/mirna-suppression-of-a-notch-repressor-directs-non-neuronal-fate-in-drosophila-mechanosensory-organs
#16
Joshua Kavaler, Hong Duan, Rajaguru Aradhya, Luis F de Navas, Brian Joseph, Boris Shklyar, Eric C Lai
Although there is abundant evidence that individual microRNA (miRNA) loci repress large cohorts of targets, large-scale knockout studies suggest that most miRNAs are phenotypically dispensable. Here, we identify a rare case of developmental cell specification that is highly dependent on miRNA control of an individual target. We observe that binary cell fate choice in the Drosophila melanogaster peripheral sensory organ lineage is controlled by the non-neuronally expressed mir-279/996 cluster, with a majority of notum sensory organs exhibiting transformation of sheath cells into ectopic neurons...
December 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29191225/landscape-and-evolution-of-tissue-specific-alternative-polyadenylation-across-drosophila-species
#17
Piero Sanfilippo, Jiayu Wen, Eric C Lai
BACKGROUND: Drosophila melanogaster has one of best-described transcriptomes of any multicellular organism. Nevertheless, the paucity of 3'-sequencing data in this species precludes comprehensive assessment of alternative polyadenylation (APA), which is subject to broad tissue-specific control. RESULTS: Here, we generate deep 3'-sequencing data from 23 developmental stages, tissues, and cell lines of D. melanogaster, yielding a comprehensive atlas of ~ 62,000 polyadenylated ends...
November 30, 2017: Genome Biology
https://www.readbyqxmd.com/read/29069479/flyatlas-2-a-new-version-of-the-drosophila-melanogaster-expression-atlas-with-rna-seq-mirna-seq-and-sex-specific-data
#18
David P Leader, Sue A Krause, Aniruddha Pandit, Shireen A Davies, Julian A T Dow
FlyAtlas 2 ( www.flyatlas2.org ) is part successor, part complement to the FlyAtlas database and web application for studying the expression of the genes of Drosophila melanogaster in different tissues of adults and larvae. Although generated in the same lab with the same fly line raised on the same diet as FlyAtlas, the FlyAtlas2 resource employs a completely new set of expression data based on RNA-Seq, rather than microarray analysis, and so it allows the user to obtain information for the expression of different transcripts of a gene...
October 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29045748/conserved-asymmetry-underpins-homodimerization-of-dicer-associated-double-stranded-rna-binding-proteins
#19
Alex Heyam, Claire E Coupland, Clément Dégut, Ruth A Haley, Nicola J Baxter, Leonhard Jakob, Pedro M Aguiar, Gunter Meister, Michael P Williamson, Dimitris Lagos, Michael J Plevin
Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding residues and instead interact with other proteins. In higher eukaryotes, the microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP) or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with Loquacious (Loqs)...
October 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040648/molecular-basis-for-asymmetry-sensing-of-sirnas-by-the-drosophila-loqs-pd-dcr-2-complex-in-rna-interference
#20
Jan-Niklas Tants, Stephanie Fesser, Thomas Kern, Ralf Stehle, Arie Geerlof, Christoph Wunderlich, Michael Juen, Christoph Hartlmüller, Romy Böttcher, Stefan Kunzelmann, Oliver Lange, Christoph Kreutz, Klaus Förstemann, Michael Sattler
RNA interference defends against RNA viruses and retro-elements within an organism's genome. It is triggered by duplex siRNAs, of which one strand is selected to confer sequence-specificity to the RNA induced silencing complex (RISC). In Drosophila, Dicer-2 (Dcr-2) and the double-stranded RNA binding domain (dsRBD) protein R2D2 form the RISC loading complex (RLC) and select one strand of exogenous siRNAs according to the relative thermodynamic stability of base-pairing at either end. Through genome editing we demonstrate that Loqs-PD, the Drosophila homolog of human TAR RNA binding protein (TRBP) and a paralog of R2D2, forms an alternative RLC with Dcr-2 that is required for strand choice of endogenous siRNAs in S2 cells...
October 13, 2017: Nucleic Acids Research
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