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      MirGeneDB 2.0: the metazoan microRNA complement

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          Abstract

          Small non-coding RNAs have gained substantial attention due to their roles in animal development and human disorders. Among them, microRNAs are special because individual gene sequences are conserved across the animal kingdom. In addition, unique and mechanistically well understood features can clearly distinguish bona fide miRNAs from the myriad other small RNAs generated by cells. However, making this distinction is not a common practice and, thus, not surprisingly, the heterogeneous quality of available miRNA complements has become a major concern in microRNA research. We addressed this by extensively expanding our curated microRNA gene database - MirGeneDB - to 45 organisms, encompassing a wide phylogenetic swath of animal evolution. By consistently annotating and naming 10,899 microRNA genes in these organisms, we show that previous microRNA annotations contained not only many false positives, but surprisingly lacked >2000 bona fide microRNAs. Indeed, curated microRNA complements of closely related organisms are very similar and can be used to reconstruct ancestral miRNA repertoires. MirGeneDB represents a robust platform for microRNA-based research, providing deeper and more significant insights into the biology and evolution of miRNAs as well as biomedical and biomarker research. MirGeneDB is publicly and freely available at http://mirgenedb.org/.

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          Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs.

          MicroRNAs (miRNAs) are a class of noncoding RNAs that post-transcriptionally regulate gene expression in plants and animals. To investigate the influence of miRNAs on transcript levels, we transfected miRNAs into human cells and used microarrays to examine changes in the messenger RNA profile. Here we show that delivering miR-124 causes the expression profile to shift towards that of brain, the organ in which miR-124 is preferentially expressed, whereas delivering miR-1 shifts the profile towards that of muscle, where miR-1 is preferentially expressed. In each case, about 100 messages were downregulated after 12 h. The 3' untranslated regions of these messages had a significant propensity to pair to the 5' region of the miRNA, as expected if many of these messages are the direct targets of the miRNAs. Our results suggest that metazoan miRNAs can reduce the levels of many of their target transcripts, not just the amount of protein deriving from these transcripts. Moreover, miR-1 and miR-124, and presumably other tissue-specific miRNAs, seem to downregulate a far greater number of targets than previously appreciated, thereby helping to define tissue-specific gene expression in humans.
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            miRBase: from microRNA sequences to function

            Abstract miRBase catalogs, names and distributes microRNA gene sequences. The latest release of miRBase (v22) contains microRNA sequences from 271 organisms: 38 589 hairpin precursors and 48 860 mature microRNAs. We describe improvements to the database and website to provide more information about the quality of microRNA gene annotations, and the cellular functions of their products. We have collected 1493 small RNA deep sequencing datasets and mapped a total of 5.5 billion reads to microRNA sequences. The read mapping patterns provide strong support for the validity of between 20% and 65% of microRNA annotations in different well-studied animal genomes, and evidence for the removal of >200 sequences from the database. To improve the availability of microRNA functional information, we are disseminating Gene Ontology terms annotated against miRBase sequences. We have also used a text-mining approach to search for microRNA gene names in the full-text of open access articles. Over 500 000 sentences from 18 542 papers contain microRNA names. We score these sentences for functional information and link them with 12 519 microRNA entries. The sentences themselves, and word clouds built from them, provide effective summaries of the functional information about specific microRNAs. miRBase is publicly and freely available at http://mirbase.org/.
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              Metazoan MicroRNAs

              MicroRNAs (miRNAs) are ∼22 nt RNAs that direct posttranscriptional repression of mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these small RNAs help sculpt the expression of most mRNAs. This article reviews advances in our understanding of the defining features of metazoan miRNAs and their biogenesis, genomics, and evolution. It then reviews how metazoan miRNAs are regulated, how they recognize and cause repression of their targets, and the biological functions of this repression, with a compilation of knockout phenotypes that shows that important biological functions have been identified for most of the broadly conserved miRNAs of mammals.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2020
                10 October 2019
                10 October 2019
                : 48
                : D1
                : D132-D141
                Affiliations
                [1 ] Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , Stockholm, Sweden
                [2 ] Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital , Oslo, Norway
                [3 ] Center for Bioinformatics, Department of Informatics, University of Oslo , Oslo, Norway
                [4 ] Department of Pathology, Institute of Clinical Medicine, University of Oslo , Oslo, Norway
                [5 ] Institute of Clinical Medicine, University of Oslo , Oslo, Norway
                [6 ] School of Life Sciences, Faculty of Health and Life Sciences, University of Nottingham , UK
                [7 ] Department of Human and Animal Genetics, The Federal Research Center Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Sciences , Novosibirsk, Russian Federation
                [8 ] Department of Genetics, Faculty of Sciences, University of Granada , Granada, Spain
                [9 ] Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital , Nydalen, Oslo, Norway
                [10 ] Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo , Oslo, Norway
                [11 ] Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital Radiumhospitalet , Oslo, Norway
                [12 ] Department of Biological Sciences, Dartmouth College , Hanover, NH, USA
                Author notes
                To whom correspondence should be addressed. Tel: +46 76 136 69 55; Fax: +46 76 136 69 55; Email: bastianfromm@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-0352-3037
                http://orcid.org/0000-0001-5127-5459
                http://orcid.org/0000-0002-9103-1077
                http://orcid.org/0000-0003-2248-3114
                http://orcid.org/0000-0001-6577-4363
                Article
                gkz885
                10.1093/nar/gkz885
                6943042
                31598695
                4a1384ce-4847-4ebf-b707-2a9af7dc4add
                © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 01 October 2019
                : 18 September 2019
                : 14 August 2019
                Page count
                Pages: 10
                Funding
                Funded by: Swedish Research Council 10.13039/501100004359
                Funded by: Southern and Eastern Norway Regional Health Authority 10.13039/501100006095
                Award ID: 2014041
                Award ID: 2018014
                Funded by: Russian Science Foundation 10.13039/501100006769
                Award ID: 18-15-00098
                Funded by: University of Nottingham 10.13039/501100000837
                Funded by: Norwegian Research Council 10.13039/501100005416
                Funded by: National Science Foundation 10.13039/100000001
                Funded by: NASA-Ames
                Funded by: Dartmouth College 10.13039/100008299
                Categories
                Database Issue

                Genetics
                Genetics

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