18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m 6A machinery component Wtap/Fl(2)d

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In this study, Knuckles et al. identified Flacc/Zc3h13 as a novel interactor of m 6A methyltransferase complex components in Drosophila and mice. They show that Flacc promotes the recruitment of the methyltransferase to mRNA by bridging Fl(2)d to the mRNA-binding factor Nito, providing novel insights into the conservation and regulation of the m 6A machinery.

          Abstract

          N 6-methyladenosine (m 6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m 6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m 6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m 6A levels and is involved in sex determination in Drosophila. We demonstrate that Flacc promotes m 6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m 6A machinery.

          Related collections

          Most cited references49

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          deepTools2: a next generation web server for deep-sequencing data analysis

          We present an update to our Galaxy-based web server for processing and visualizing deeply sequenced data. Its core tool set, deepTools, allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches. Since we first described our deepTools Galaxy server in 2014, we have implemented new solutions for many requests from the community and our users. Here, we introduce significant enhancements and new tools to further improve data visualization and interpretation. deepTools continue to be open to all users and freely available as a web service at deeptools.ie-freiburg.mpg.de. The new deepTools2 suite can be easily deployed within any Galaxy framework via the toolshed repository, and we also provide source code for command line usage under Linux and Mac OS X. A public and documented API for access to deepTools functionality is also available.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The Perseus computational platform for comprehensive analysis of (prote)omics data.

            A main bottleneck in proteomics is the downstream biological analysis of highly multivariate quantitative protein abundance data generated using mass-spectrometry-based analysis. We developed the Perseus software platform (http://www.perseus-framework.org) to support biological and biomedical researchers in interpreting protein quantification, interaction and post-translational modification data. Perseus contains a comprehensive portfolio of statistical tools for high-dimensional omics data analysis covering normalization, pattern recognition, time-series analysis, cross-omics comparisons and multiple-hypothesis testing. A machine learning module supports the classification and validation of patient groups for diagnosis and prognosis, and it also detects predictive protein signatures. Central to Perseus is a user-friendly, interactive workflow environment that provides complete documentation of computational methods used in a publication. All activities in Perseus are realized as plugins, and users can extend the software by programming their own, which can be shared through a plugin store. We anticipate that Perseus's arsenal of algorithms and its intuitive usability will empower interdisciplinary analysis of complex large data sets.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq.

              An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks--around stop codons and within long internal exons--and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.
                Bookmark

                Author and article information

                Journal
                Genes Dev
                Genes Dev
                genesdev
                genesdev
                GAD
                Genes & Development
                Cold Spring Harbor Laboratory Press
                0890-9369
                1549-5477
                1 March 2018
                1 March 2018
                : 32
                : 5-6
                : 415-429
                Affiliations
                [1 ]Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland;
                [2 ]University of Basel, Basel 4002, Switzerland;
                [3 ]Institute of Molecular Biology, 55128 Mainz, Germany;
                [4 ]School of Life Science, Faculty of Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom;
                [5 ]School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom;
                [6 ]Institute of Pharmacy and Biochemistry, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany;
                [7 ]Bioinformatics Core Facility, Institute of Molecular Biology, 55128 Mainz, Germany;
                [8 ]Swiss Institute of Bioinformatics, Basel 4058, Switzerland;
                [9 ]Laboratory of Cell Biology and Neurobiology, Department of Animal Biology, University of Pavia, Pavia 27100, Italy;
                [10 ]Faculty of Biology, Johannes Gutenberg University of Mainz, 55128 Mainz, Germany
                Author notes
                [11]

                Present address: Department of Molecular Mechanisms of Disease, University of Zurich, 8057 Zürich, Switzerland.

                [12]

                These authors contributed equally to this work.

                Article
                8711660
                10.1101/gad.309146.117
                5900714
                29535189
                2db79914-4b9d-49c1-a0fc-ed38155a0f44
                © 2018 Knuckles et al.; Published by Cold Spring Harbor Laboratory Press

                This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 October 2017
                : 12 February 2018
                Page count
                Pages: 15
                Funding
                Funded by: Deutsche Forschungsgemeinschaft , open-funder-registry 10.13039/501100001659;
                Award ID: RO 4681/5-1
                Funded by: Epitran COST action
                Award ID: CA16120
                Funded by: Novartis Research Foundation , open-funder-registry 10.13039/100008273;
                Funded by: Swiss Science Foundation National Centre of Competence in Research RNA and Disease
                Award ID: 141735
                Funded by: Biotechnology and Biological Sciences Research Council , open-funder-registry 10.13039/501100000268;
                Funded by: DFG , open-funder-registry 10.13039/501100001659;
                Award ID: SPP1784
                Categories
                Research Paper

                zc3h13,flacc,m6a,methyltransferase complex,rna modifications,sex determination

                Comments

                Comment on this article