28
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Rewriting the transcriptome: adenosine-to-inosine RNA editing by ADARs

      review-article
      1 , 2 , , 3 ,
      Genome Biology
      BioMed Central

      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

          One of the most prevalent forms of post-transcritpional RNA modification is the conversion of adenosine nucleosides to inosine (A-to-I), mediated by the ADAR family of enzymes. The functional requirement and regulatory landscape for the majority of A-to-I editing events are, at present, uncertain. Recent studies have identified key in vivo functions of ADAR enzymes, informing our understanding of the biological importance of A-to-I editing. Large-scale studies have revealed how editing is regulated both in cis and in trans. This review will explore these recent studies and how they broaden our understanding of the functions and regulation of ADAR-mediated RNA editing.

          Related collections

          Most cited references116

          • Record: found
          • Abstract: found
          • Article: not found

          The evolutionary landscape of alternative splicing in vertebrate species.

          How species with similar repertoires of protein-coding genes differ so markedly at the phenotypic level is poorly understood. By comparing organ transcriptomes from vertebrate species spanning ~350 million years of evolution, we observed significant differences in alternative splicing complexity between vertebrate lineages, with the highest complexity in primates. Within 6 million years, the splicing profiles of physiologically equivalent organs diverged such that they are more strongly related to the identity of a species than they are to organ type. Most vertebrate species-specific splicing patterns are cis-directed. However, a subset of pronounced splicing changes are predicted to remodel protein interactions involving trans-acting regulators. These events likely further contributed to the diversification of splicing and other transcriptomic changes that underlie phenotypic differences among vertebrate species.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2.

            RNA editing by site-selective deamination of adenosine to inosine alters codons and splicing in nuclear transcripts, and therefore protein function. ADAR2 (refs 7, 8) is a candidate mammalian editing enzyme that is widely expressed in brain and other tissues, but its RNA substrates are unknown. Here we have studied ADAR2-mediated RNA editing by generating mice that are homozygous for a targeted functional null allele. Editing in ADAR2-/- mice was substantially reduced at most of 25 positions in diverse transcripts; the mutant mice became prone to seizures and died young. The impaired phenotype appeared to result entirely from a single underedited position, as it reverted to normal when both alleles for the underedited transcript were substituted with alleles encoding the edited version exonically. The critical position specifies an ion channel determinant, the Q/R site, in AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor GluR-B pre-messenger RNA. We conclude that this transcript is the physiologically most important substrate of ADAR2.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Messenger RNA modifications: Form, distribution, and function.

              RNA contains more than 100 distinct modifications that promote the functions of stable noncoding RNAs in translation and splicing. Recent technical advances have revealed widespread and sparse modification of messenger RNAs with N(6)-methyladenosine (m(6)A), 5-methylcytosine (m(5)C), and pseudouridine (Ψ). Here we discuss the rapidly evolving understanding of the location, regulation, and function of these dynamic mRNA marks, collectively termed the epitranscriptome. We highlight differences among modifications and between species that could instruct ongoing efforts to understand how specific mRNA target sites are selected and how their modification is regulated. Diverse molecular consequences of individual m(6)A modifications are beginning to be revealed, but the effects of m(5)C and Ψ remain largely unknown. Future work linking molecular effects to organismal phenotypes will broaden our understanding of mRNA modifications as cell and developmental regulators.
                Bookmark

                Author and article information

                Contributors
                cwalkley@svi.edu.au
                jin.billy.li@stanford.edu
                Journal
                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1474-7596
                1474-760X
                30 October 2017
                30 October 2017
                2017
                : 18
                : 205
                Affiliations
                [1 ]ISNI 0000 0004 0626 201X, GRID grid.1073.5, St Vincent’s Institute of Medical Research, ; Fitzroy, Victoria 3065 Australia
                [2 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Medicine, St Vincent’s Hospital, , University of Melbourne, ; Fitzroy, Victoria 3065 Australia
                [3 ]ISNI 0000000419368956, GRID grid.168010.e, Department of Genetics, , Stanford University, ; Stanford, CA 94305 USA
                Article
                1347
                10.1186/s13059-017-1347-3
                5663115
                29084589
                59b0aee7-d5ea-4bc8-895b-35a0f2b9a47b
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1102006
                Funded by: FundRef http://dx.doi.org/10.13039/501100000951, Cancer Council Victoria;
                Funded by: FundRef http://dx.doi.org/10.13039/100008018, Victorian Cancer Agency;
                Funded by: FundRef http://dx.doi.org/10.13039/501100003747, Department of Health, State Government of Victoria;
                Award ID: OIS to St Vincent's Institute
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01GM102484, R01GM104215, and R01MH115080
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000863, Ellison Medical Foundation;
                Funded by: FundRef http://dx.doi.org/10.13039/100005492, Stanford University;
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Genetics
                Genetics

                Comments

                Comment on this article