20 results on '"miRNA function"'
Search Results
2. Genome-Wide Analysis of microRNA Expression Profile in Roots and Leaves of Three Wheat Cultivars under Water and Drought Conditions.
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Gómez-Martín, Cristina, Zhou, Hui, Medina, José María, Aparicio-Puerta, Ernesto, Shi, Bujun, and Hackenberg, Michael
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GENE expression , *WHEAT , *NON-coding RNA , *DROUGHTS , *CULTIVARS , *MICRORNA - Abstract
Wheat is one of the most important food sources on Earth. MicroRNAs (miRNAs) play important roles in wheat productivity. To identify wheat miRNAs as well as their expression profiles under drought condition, we constructed and sequenced small RNA (sRNA) libraries from the leaves and roots of three wheat cultivars (Kukri, RAC875 and Excalibur) under water and drought conditions. A total of 636 known miRNAs and 294 novel miRNAs were identified, of which 34 miRNAs were tissue- or cultivar-specific. Among these, 314 were significantly regulated under drought conditions. miRNAs that were drought-regulated in all cultivars displayed notably higher expression than those that responded in a cultivar-specific manner. Cultivar-specific drought response miRNAs were mainly detected in roots and showed significantly different drought regulations between cultivars. By using wheat degradome library, 6619 target genes were identified. Many target genes were strongly enriched for protein domains, such as MEKHLA, that play roles in drought response. Targeting analysis showed that drought-downregulated miRNAs targeted more genes than drought-upregulated miRNAs. Furthermore, such genes had more important functions. Additionally, the genes targeted by drought-downregulated miRNAs had multiple interactions with each other, while the genes targeted by drought-upregulated miRNAs had no interactions. Our data provide valuable information on wheat miRNA expression profiles and potential functions in different tissues, cultivars and drought conditions. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Comprehensive, integrative genomic analysis of microRNA expression profiles in different tissues of two wheat cultivars with different traits.
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Gómez-Martín, Cristina, Zhou, Hui, Medina, José Maria, Aparicio-Puerta, Ernesto, Hackenberg, Michael, and Shi, Bujun
- Abstract
Wheat is one of the most important food sources on Earth. MicroRNAs (miRNA) play important roles in wheat productivity. To identify wheat miRNAs, we constructed and sequenced sRNA libraries from leaves and roots of two wheat cultivars (RAC875 and Kukri) with many different traits. Given that available miRNA wheat complement in the plant-specific database PmiREN () does not include root tissues and root-associated miRNAs might thus be missing, we performed first the prediction of novel miRNAs using the sRNAbench tool. We found a total of 150 putatively novel miRNA genes with expression of both arms from 289 unique mature sequences and nearly 30% of all miRNA reads in roots corresponded to novel miRNAs. In contrast, this figure in leaves dropped to under 3%, confirming the undersampling of roots in the complement of known miRNAs. By using 120 publicly available wheat datasets, 598 Zea mays small RNA libraries, 64 plant species genomes, wheat degradome library, and functional enrichment analysis, a subset of novel miRNAs were confirmed as bona-fide miRNAs. Of the total 605 miRNAs identified in this study inclusive of 316 known miRNAs, 528 miRNAs were shared by both cultivars, 429 miRNAs were shared by both root tissues and 329 miRNAs were shared by both leaf tissues. In addition, 32 miRNAs were specific to Kukri while 45 miRNAs were specific to RAC875. These miRNAs had diverse functions, such as regulation of gene transcription, protein translation, energy metabolism, and cell cycle progression. Our data provide a genome-wide miRNA expression profile in these two wheat cultivars and help functional studies of wheat genomics. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Induced miR‐99a expression represses Mtor cooperatively with miR‐150 to promote regulatory T‐cell differentiation
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Warth, Sebastian C, Hoefig, Kai P, Hiekel, Anian, Schallenberg, Sonja, Jovanovic, Ksenija, Klein, Ludger, Kretschmer, Karsten, Ansel, K Mark, and Heissmeyer, Vigo
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Biomedical and Clinical Sciences ,Immunology ,Biotechnology ,Genetics ,1.1 Normal biological development and functioning ,3' Untranslated Regions ,Animals ,Base Sequence ,CD4-Positive T-Lymphocytes ,Cell Differentiation ,Cells ,Cultured ,DEAD-box RNA Helicases ,Gene Expression Regulation ,Gene Regulatory Networks ,Green Fluorescent Proteins ,Mice ,Inbred C57BL ,Mice ,Transgenic ,MicroRNAs ,Molecular Sequence Data ,Ribonuclease III ,T-Lymphocytes ,Regulatory ,TOR Serine-Threonine Kinases ,Tretinoin ,miRNA function ,T-cell differentiation ,Treg cells ,T‐cell differentiation ,Biological Sciences ,Information and Computing Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Peripheral induction of regulatory T (Treg) cells provides essential protection from inappropriate immune responses. CD4(+) T cells that lack endogenous miRNAs are impaired to differentiate into Treg cells, but the relevant miRNAs are unknown. We performed an overexpression screen with T-cell-expressed miRNAs in naive mouse CD4(+) T cells undergoing Treg differentiation. Among 130 candidates, the screen identified 29 miRNAs with a negative and 10 miRNAs with a positive effect. Testing reciprocal Th17 differentiation revealed specific functions for miR-100, miR-99a and miR-10b, since all of these promoted the Treg and inhibited the Th17 program without impacting on viability, proliferation and activation. miR-99a cooperated with miR-150 to repress the expression of the Th17-promoting factor mTOR. The comparably low expression of miR-99a was strongly increased by the Treg cell inducer "retinoic acid", and the abundantly expressed miR-150 could only repress Mtor in the presence of miR-99a. Our data suggest that induction of Treg cell differentiation is regulated by a miRNA network, which involves cooperation of constitutively expressed as well as inducible miRNAs.
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- 2015
5. Conservation, Divergence, and Abundance of MiRNAs and Their Effect in Plants
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de Fátima Rosas-Cárdenas, Flor, de Folter, Stefan, Barciszewski, Jan, Series editor, Rajewsky, Nikolaus, Series editor, Erdmann, Volker A., Founding editor, and Jurga, Stefan, editor
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- 2017
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6. Analyses of MiRNA Functions in Maize Using a Newly Developed ZMBJ-CMV-2bN81-STTM Vector
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Xuedong Liu, Sijia Liu, Rong Wang, Xi Chen, Zaifeng Fan, Boming Wu, and Tao Zhou
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plant endogenous microRNAs ,virus-based miRNA suppression ,cucumber mosaic virus ,high-throughput ,miRNA function ,Plant culture ,SB1-1110 - Abstract
Endogenous microRNAs (miRNAs) play pivotal roles in plant development and responses to various biotic or abiotic stresses. Up to now, more than 500 maize miRNAs have been identified. However, functions of these identified miRNAs remained largely unknown due mainly to the lack of rapid and reliable tools. We previously reported a cucumber mosaic virus strain ZMBJ (ZMBJ-CMV)-based gene silencing vector for rapid and efficient gene function studies in maize lines with agronomical importance. Because ZMBJ-CMV induces very mild disease symptoms but strong gene silencing in maize, we decided to further modify this vector to suppress miRNA expressions in maize. The newly developed ZMBJ-CMV-2bN81-STTM vector expresses a short tandem target mimic (STTM) containing two target-mimic sequences separated by a short spacer sequence. Our results showed that ZMBJ-CMV-2bN81-STTM can be used to investigate miRNA function in Nicotiana benthamiana and maize seedlings. The ZMBJ-CMV-2bN81-STTM-based downregulation of Nbe-miR165/166 or Nbe-miR159 induced specific and strong miRNA-sequestering phenotypes, and increased the expressions of their predicted target genes. For maize, the ZMBJ-CMV-2bN81-STTM based downregulation of zma-miR167 or zma-miR482 caused a decrease of lateral roots growth and a plant stunting phenotypes, respectively. In both cases, the target genes of zma-miR167- or zma-miR482 were increased significantly. Thus, we consider ZMBJ-CMV based VbMS system as a useful tool for high-throughput investigations of miRNA functions in maize.
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- 2019
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7. The Role of Ago2 in microRNA Biogenesis: An Investigation of miR-21
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Fogel, Gary B., Lopez, Ana D., Kai, Zoya, King, Charles C., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Lones, Michael, editor, Tyrrell, Andy, editor, Smith, Stephen, editor, and Fogel, Gary, editor
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- 2015
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8. Analyses of MiRNA Functions in Maize Using a Newly Developed ZMBJ-CMV-2bN81-STTM Vector.
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Liu, Xuedong, Liu, Sijia, Wang, Rong, Chen, Xi, Fan, Zaifeng, Wu, Boming, and Zhou, Tao
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NICOTIANA benthamiana ,MICRORNA ,CORN ,GENE silencing ,CUCUMBER mosaic virus ,STUNTED growth ,ROOT growth ,MOSAIC viruses - Abstract
Endogenous microRNAs (miRNAs) play pivotal roles in plant development and responses to various biotic or abiotic stresses. Up to now, more than 500 maize miRNAs have been identified. However, functions of these identified miRNAs remained largely unknown due mainly to the lack of rapid and reliable tools. We previously reported a cucumber mosaic virus strain ZMBJ (ZMBJ-CMV)-based gene silencing vector for rapid and efficient gene function studies in maize lines with agronomical importance. Because ZMBJ-CMV induces very mild disease symptoms but strong gene silencing in maize, we decided to further modify this vector to suppress miRNA expressions in maize. The newly developed ZMBJ-CMV-2b
N81 -STTM vector expresses a short tandem target mimic (STTM) containing two target-mimic sequences separated by a short spacer sequence. Our results showed that ZMBJ-CMV-2bN81 -STTM can be used to investigate miRNA function in Nicotiana benthamiana and maize seedlings. The ZMBJ-CMV-2bN81 -STTM-based downregulation of Nbe-miR165/166 or Nbe-miR159 induced specific and strong miRNA-sequestering phenotypes, and increased the expressions of their predicted target genes. For maize, the ZMBJ-CMV-2bN81 -STTM based downregulation of zma-miR167 or zma-miR482 caused a decrease of lateral roots growth and a plant stunting phenotypes, respectively. In both cases, the target genes of zma-miR167- or zma-miR482 were increased significantly. Thus, we consider ZMBJ-CMV based VbMS system as a useful tool for high-throughput investigations of miRNA functions in maize. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Web Resources for microRNA Research
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Schmitz, Ulf, Wolkenhauer, Olaf, Schmitz, Ulf, editor, Wolkenhauer, Olaf, editor, and Vera, Julio, editor
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- 2013
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10. Small-Molecule Regulation of MicroRNA Function
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Connelly, Colleen M., Deiters, Alexander, and Alahari, Suresh, editor
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- 2013
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11. MicroRNAs
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Cheung, Onpan, Sanyal, Arun J., Dufour, Jean-Francois, editor, and Clavien, Pierre-Alain, editor
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- 2010
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12. Identification and expression analysis of microRNAs in worker caste termites of Coptotermes formosanus and Reticulitermes speratus.
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Itakura, Shuji, Hattori, Kazuya, and Umezawa, Kiwamu
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A total of 114 microRNAs (miRNAs) were identified for Coptotermes formosanus workers, while a total of 97 miRNAs were identified for Reticulitermes speratus workers, of which 91 were common in C. formosanus and R. speratus . While the relationship between miRNA expression levels in C. formosanus and R. speratus workers had a strong positive correlation, considerable difference in miRNA expressions between C. formosanus and R. speratus was observed. Among the miRNAs up-regulated in C. formosanus workers, miR-11-3p showed the highest expression increase of 2.30 fold, while miR-13b-3p showed the highest expression increase of 5.16 fold among the up-regulated miRNAs in R. speratus workers. Workers of C. formosanus and R. speratus seem to use different miRNAs, miR-11-3p in C. formosanus or miR-13b-3p in R. speratus , to regulate homeodomain transcription factor genes, araucan , caupolican , and nubbin , basic helix-loop-helix (bHLH) transcription factor genes, spineless and E(spl)m3-HLH , and zinc finger transcription factor gene, castor . [ABSTRACT FROM AUTHOR]
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- 2018
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13. Anti-miRNA Antisense Oligonucleotides Technology
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Wang, Zhiguo and Wang, Zhiguo
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- 2009
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14. New Insight into microRNA Functions in Cancer: Oncogene–microRNA–Tumor Suppressor Gene Network
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Kecheng Zhou, Minxia Liu, and Yi Cao
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oncogene–microRNA–tumor suppressor gene network ,miRNA function ,cancer ,oncogenes ,tumor suppressor genes ,Biology (General) ,QH301-705.5 - Abstract
Tumorigenesis is a multi-step and complex process with multi-factors involved. Deregulated oncogenes and tumor suppressor genes (TSGs) induced by genetic and epigenetic factors are considered as the driving force in the development and progression of cancer. Besides, microRNAs (miRNAs) act vital roles in tumorigenesis through regulating some oncogenes and TSGs. Interestingly, miRNAs are also regulated by oncogenes and TSGs. Considering the entangled regulation, here we propose a new insight into these regulation relationships in cancer: oncogene–miRNA–TSG network, which further emphasizes roles of miRNA, as well as highlights the network regulation among oncogene, miRNA, and TSG during tumorigenesis. The oncogene–miRNA–TSG network demonstrates that oncogenes and TSGs not only show functional synergy, but also there are regulatory relationships among oncogenes and TSGs during tumorigenesis, which could be mediated by miRNAs. In view of the oncogene–miRNA–TSG network involved in many oncogenes, miRNAs, and TSGs, as well as occurring in various tumor types, the anomaly of this network may be a common event in cancers and participates in tumorigenesis. This hypothesis broadens horizons of molecular mechanisms underlying tumorigenesis, and may provide a new promising venue for the prediction, diagnosis, and even therapy of cancer.
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- 2017
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15. Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo
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Magdalena Materniak-Kornas, Juan Tan, Anke Heit-Mondrzyk, Agnes Hotz-Wagenblatt, and Martin Löchelt
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bovine foamy virus ,bfv ,foamy virus ,spuma virus ,model system ,animal model ,animal experiment ,mirna function ,gene expression ,antiviral host restriction ,Microbiology ,QR1-502 - Abstract
The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts [1]. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and thus do not pose medical problems to humans and livestock or companion animals. A robust lab animal model is not available or is a lab animal a natural host of a FV. Due to this, research is limited and often focused on the simian FVs with their well-established zoonotic potential. The authors of this review and their groups have conducted several studies on bovine FV (BFV) in the past with the intention of (i) exploring the risk of zoonotic infection via beef and raw cattle products, (ii) studying a co-factorial role of BFV in different cattle diseases with unclear etiology, (iii) exploring unique features of FV molecular biology and replication strategies in non-simian FVs, and (iv) conducting animal studies and functional virology in BFV-infected calves as a model for corresponding studies in primates or small lab animals. These studies gained new insights into FV-host interactions, mechanisms of gene expression, and transcriptional regulation, including miRNA biology, host-directed restriction of FV replication, spread and distribution in the infected animal, and at the population level. The current review attempts to summarize these findings in BFV and tries to connect them to findings from other FVs.
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- 2019
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16. From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways
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German Osmak, O O Favorova, Ivan Kiselev, and Natalia Baulina
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0301 basic medicine ,rho GTP-Binding Proteins ,RHOA ,MAPK3 ,Apoptosis ,CDC42 ,heart ,030204 cardiovascular system & hematology ,Catalysis ,Article ,miR-375 ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Rho-GTPases ,Mir-375 ,microRNA ,Humans ,Gene Regulatory Networks ,Physical and Theoretical Chemistry ,Molecular Biology ,Gene ,lcsh:QH301-705.5 ,network analysis ,Spectroscopy ,biology ,Myocardium ,Organic Chemistry ,RNA ,General Medicine ,Actins ,Computer Science Applications ,Cell biology ,miRNA function ,MicroRNAs ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Gene Expression Regulation ,Organ Specificity ,biology.protein ,RNA Interference ,Signal transduction ,Function (biology) ,Signal Transduction - Abstract
MicroRNAs (miRNAs) are short single-stranded non-coding RNA molecules, which are involved in regulation of main biological processes, such as apoptosis, cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases and data on its function in myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signalling pathways.We implemented our algorithm for miRNA function prediction into Python module, which is available at GitHub (https://github.com/GJOsmak/miRNET)
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- 2020
17. MicroRNAs – micro in size but macro in function.
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Singh, Sunit K., Pal Bhadra, Manika, Girschick, Hermann J., and Bhadra, Utpal
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MESSENGER RNA , *ONCOGENES , *ORIGIN of life , *APOPTOSIS , *ONCOGENIC viruses , *HEALTH - Abstract
MicroRNAs (miRNAs) are endogenous small RNAs that can regulate target mRNAs by binding to their 3′-UTRs. A single miRNA can regulate many mRNA targets, and several miRNAs can regulate a single mRNA. These have been reported to be involved in a variety of functions, including developmental transitions, neuronal patterning, apoptosis, adipogenesis metabolism and hematopoiesis in different organisms. Many oncogenes and tumor suppressor genes are regulated by miRNAs. Studies conducted in the past few years have demonstrated the possible association between miRNAs and several human malignancies and infectious diseases. In this article, we have focused on the mechanism of miRNA biogenesis and the role of miRNAs in human health and disease. [ABSTRACT FROM AUTHOR]
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- 2008
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18. From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways.
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Osmak, German, Kiselev, Ivan, Baulina, Natalia, and Favorova, Olga
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GENE regulatory networks , *NON-coding RNA , *RNA , *MICRORNA , *HEART diseases , *ACTIN - Abstract
MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, which are involved in the regulation of main biological processes, such as apoptosis or cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study, we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases, and data on its function in the myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signaling pathways. We implemented our algorithm for miRNA function prediction into a Python module, which is available at GitHub. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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19. Regulation der microRNA Funktion in neuronaler Entwicklung durch den Transkriptionscoaktivator Ncoa3
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Störchel, Peter and Schratt, Gerhard (Prof. Dr.)
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dendritic spine ,microRNA, miRNA ,Neuron ,Ncoa3 ,miRNS ,dendrite ,SRC3, Ago2 ,miRNA function ,Medizin, Gesundheit ,Nervenzelle ,AIB1 ,transkription ,Medical sciences, Medicine ,ddc:610 - Abstract
Tightly orchestrated gene expression programs enable proper neuronal development as well as the synaptic adaptations that are responsible for learning and memory processes. MicroRNAs (miRNAs) are a class of short regulatory RNA molecules which negatively affect the translation of target mRNAs, thereby contributing to the regulation of gene expression during brain development and cognitive functions. In the present cumulative thesis, I summarize my contributions to three research articles which describe the impact of specific miRNAs and an upstream regulator, the nuclear receptor co-activator 3 (Ncoa3), on neuronal growth and synaptic function. In the first publication, we identified miR-181a to be enriched at synaptic sites of the nucleus accumbens, a brain region of the dopaminergic mesolimbic system which is involved in the development of addiction. Using primary neurons, we demonstrated that miR-181a directly regulates the expression of the AMPA-receptor (AMPA-R) subunit GluA2. Neuromorphological analysis and electrophysiological measurements showed that miR-181a affects transmission at excitatory synapses. Dopamine signaling stimulated the expression of miR-181a which further influenced the dopamine-dependent control of GluA2 expression. Treatment of mice with several drugs of abuse specifically upregulated miR-181a levels in different brain regions. Taken together, this publication established miR-181a as novel regulator of synaptic efficacy and in the context of the present literature as a potential modulator of addiction behavior. Based on previous findings that showed the synaptic localization of miR-137 and that identified mutations in the MIR137 gene associated with schizophrenia and cognitive disabilities, we investigated the postsynaptic functions of miR-137 in the second publication. Manipulations of miR-137 expression provided evidence that the AMPA-R subunit GluA1 mRNA is a direct target of miR-137. Intriguingly, morphological and electrophysiological measurements revealed that miR-137 regulates the number but not the strength of excitatory synapses. MiR-137 further promoted the formation of silent synapses, since miR-137 manipulations affected AMPA-R-, but not NMDA-receptor (NMDA-R)-dependent currents. Furthermore, induction of miR-137 expression was required for mGluR-dependent long term depression (LTD). Therefore, this research article provides experimental support for a postsynaptic function of miR-137 in the regulation of synapse formation and plasticity, with possible implications for schizophrenia and cognitive disabilities. In the third publication, which includes the main part of my PhD project, 10 novel regulators of miRNA-dependent gene silencing in neurons were identified by performing an RNAi-based screen. One of the newly ascertained proteins was Ncoa3, a transcription co-activator whose function in hippocampal neurons was not studied. Reporter gene assays showed that Ncoa3 was required for miRNA-mediated repression of a specific set of miRNA target genes, including Limk1. In addition, Ncoa3-knockdown increased endogenous Limk1 protein levels and interfered with miR-134-induced spine shrinkage. At the same time, Ncoa3 deficiency by itself reduced the size of dendritic spines and the amplitude of miniature excitatory postsynaptic currents (mEPSCs) while it stimulated dendrite growth. The latter phenotype was dependent on proper miRNA-expression. Ago2 is a central effector of miRNA repression and we established it further as a direct transcriptional target gene of Ncoa3. Epistasis experiments confirmed that both impaired dendritogenesis and miRNA function upon Ncoa3 knockdown were a result of reduced Ago2 expression. Thus, this publication uncovered a novel transcriptional mechanism for the control of miRNA-dependent repression during neuronal development. In summary, these findings decipher neuronal gene expression programs which control synaptic adaptations and thus are potentially involved in learning and memory processes., Präzise koordinierte Genexpressionsprogramme ermöglichen korrekte neuronale Entwicklung und synaptische Anpassungen, die für Lern- und Gedächtnisprozesse verantwortlich sind. MicroRNAs (miRNAs) sind eine Klasse kurzer regulatorischer RNA-Moleküle, welche die Translation von spezifischen Ziel-mRNAs unterdrücken und dadurch zur Regulation der Genexpression während der Entwicklung des Gehirns und kognitiver Fähigkeiten beitragen. In der vorliegenden kumulativen Dissertation fasse ich meinen Beitrag zu drei Forschungsartikeln zusammen. Sie beschreiben den Einfluss von bestimmten miRNAs, sowie eines vorgeschalteten Regulators (Nuclear receptor co-activator 3 (Ncoa3)) auf neuronales Wachstum und synaptische Funktion. In der ersten Veröffentlichung entdecken wir eine Anreicherung von miR-181a an Synapsen des Nucleus Accumbens, einer Hirnregion des dopaminergen mesolimbischen Systems, die an der Entwicklung von Suchterkrankungen beteiligt ist. Mittels primärer Neuronen wiesen wir nach, dass miR-181a die Expression der AMPA-Rezeptor(AMPA-R)-Untereinheit GluA2 direkt reguliert. Neuromorphologische Analysen und elektrophysiologische Messungen zeigten zudem, dass miR-181a die Reizübertragung an exzitatorischen Synapsen beeinflusst. Aktivierung des Dopamin-Signalwegs stimulierte die Expression von miR-181a, was sich wiederum auf die Dopamin-abhängige Kontrolle der GluA2 Expression auswirkte. Die Gabe von unterschiedlichen psychoaktiven Substanzen führte bei Mäusen ebenfalls zu einer spezifischen Erhöhung der miR-181a Expression in verschiedenen Hirnregionen. Zusammengefasst etabliert diese Veröffentlichung miR-181a als neuen Regulator von synaptischer Übertragung und im Kontext aktueller Literatur als potentiellen Modulator von Suchtverhalten. Basierend auf früheren Befunden, welche die synaptische Lokalisierung von miR-137 zeigten, und eine Assoziation von Mutationen im MIR137 Gen mit Schizophrenie und geistiger Behinderung identifizierten, untersuchten wir in der zweiten Veröffentlichung die postsynaptische Funktion von miR-137. Einflussnahme auf die miR-137 Expressionslevels belegte, dass die AMPA-R-Untereinheit GluA1 mRNA ein direktes Ziel von miR-137 ist. Interessanterweise zeigten morphologische und elektrophysiologische Messungen, dass miR-137 nur die Anzahl, nicht jedoch die Stärke von exzitatorischen Synapsen reguliert. Ferner begünstigte miR-137 die Bildung von stummen Synapsen, da veränderte miR-137 Expression zwar AMPA-R-abhängige, nicht jedoch NMDA-Rezeptor(NMDA-R)-abhängige Ströme beeinflusste. Außerdem war der Anstieg von miR-137 notwendig für mGluR-abhängige Langzeit-Depression (LTD). Diese Publikation untermauert somit eine postsynaptische Funktion von miR-137 in der Regulation von Synapsenbildung und –plastizität, sowie eine damit verbundene mögliche Bedeutung für Schizophrenie und geistige Behinderung. In der dritten Veröffentlichung, die den Hauptteil meiner Doktorarbeit beinhaltet, wurden mittels einem RNAi-basierten Screen zehn neue Regulatoren der miRNA-abhängiger Geneexpressionshemmung in Neuronen identifiziert. Eines der neu ermittelten Proteine war Ncoa3, ein Transkriptionscoaktivator dessen Funktion in Hippocampus-Neuronen bislang noch nicht untersucht war. Reportergen-Assays zeigten, dass Ncoa3 für miRNA-vermittelte Repression bei einer spezifischen Gruppe von miRNA-Zielgenen, inklusive Limk1, erforderlich ist. Zusätzlich hatte Ncoa3-knockdown zur Folge, dass endogene Limk1 Proteinmengen erhöht waren, und dass das miR-134-induzierte Schrumpfen von dendritischen Dornfortsätzen gestört war. Alleinige Ncoa3-Defizienz war zudem ausreichend die Größe von dendritischen Dornfortsätzen und die Amplitude von Miniatur exzitatorischen postsynaptischen Strömen (mEPSCs) zu reduzieren, während sie das Dendritenwachstum stimulierte. Dieser letztere Phänotyp war abhängig von ordnungsgemäßer miRNA-Expression. Ago2 ist ein zentraler Effektor von miRNA-Repression und wir etablierten es ferner als direktes transkriptionelles Zielgen von Ncoa3. Epistase-Experimente bestätigten, dass sowohl das durch Ncoa3-knockdown beeinträchtigte Dendritenwachstum, als auch die gestörte miRNA-Funktion, ein Ergebnis der reduzierten Ago2 Expression ist. Folglich enthüllt diese Veröffentlichung einen neuen transkriptionellen Mechanismus für die Kontrolle von miRNA-abhängiger Repression in neuronaler Entwicklung. Zusammenfassend entziffern diese Befunde neuronale Genexpressionsprogramme, die synaptische Anpassungen kontrollieren und so möglicherweise in Lern- und Gedächtnisprozessen involviert sind.
- Published
- 2016
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20. Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo.
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Materniak-Kornas, Magdalena, Tan, Juan, Heit-Mondrzyk, Anke, Hotz-Wagenblatt, Agnes, and Löchelt, Martin
- Subjects
FOAMY viruses ,LABORATORY animals ,CATTLE diseases ,RETROVIRUS diseases ,BEEF cattle ,ETIOLOGY of diseases ,MOLECULAR biology ,MYCOPLASMA bovis - Abstract
The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and thus do not pose medical problems to humans and livestock or companion animals. A robust lab animal model is not available or is a lab animal a natural host of a FV. Due to this, research is limited and often focused on the simian FVs with their well-established zoonotic potential. The authors of this review and their groups have conducted several studies on bovine FV (BFV) in the past with the intention of (i) exploring the risk of zoonotic infection via beef and raw cattle products, (ii) studying a co-factorial role of BFV in different cattle diseases with unclear etiology, (iii) exploring unique features of FV molecular biology and replication strategies in non-simian FVs, and (iv) conducting animal studies and functional virology in BFV-infected calves as a model for corresponding studies in primates or small lab animals. These studies gained new insights into FV-host interactions, mechanisms of gene expression, and transcriptional regulation, including miRNA biology, host-directed restriction of FV replication, spread and distribution in the infected animal, and at the population level. The current review attempts to summarize these findings in BFV and tries to connect them to findings from other FVs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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