1. Genetics and Genomics
  2. Neuroscience
Download icon

The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing

  1. Shahar Alon
  2. Sandra C Garrett
  3. Erez Y Levanon
  4. Sara Olson
  5. Brenton R Graveley
  6. Joshua J C Rosenthal
  7. Eli Eisenberg  Is a corresponding author
  1. Tel Aviv University, Israel
  2. University of Connecticut Health Center, United States
  3. Bar-Ilan University, Israel
  4. University of Puerto Rico Medical Sciences Campus, Puerto Rico
Short Report
  • Cited 62
  • Views 11,129
  • Annotations
Cite this article as: eLife 2015;4:e05198 doi: 10.7554/eLife.05198

Abstract

RNA editing by adenosine deamination alters genetic information from the genomic blueprint. When it recodes mRNAs, it gives organisms the option to express diverse, functionally distinct, protein isoforms. All eumetazoans, from cnidarians to humans, express RNA editing enzymes. However, transcriptome-wide screens have only uncovered about 25 transcripts harboring conserved recoding RNA editing sites in mammals and several hundred recoding sites in Drosophila. These studies on few established models have led to the general assumption that recoding by RNA editing is extremely rare. Here we employ a novel bioinformatic approach with extensive validation to show that the squid Doryteuthis pealeii recodes proteins by RNA editing to an unprecedented extent. We identify 57,108 recoding sites in the nervous system, affecting the majority of the proteins studied. Recoding is tissue-dependent, and enriched in genes with neuronal and cytoskeletal functions, suggesting it plays an important role in brain physiology.

Article and author information

Author details

  1. Shahar Alon

    George S Wise Faculty of Life Sciences, Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Sandra C Garrett

    Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Erez Y Levanon

    Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Sara Olson

    Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Brenton R Graveley

    Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Joshua J C Rosenthal

    Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
    Competing interests
    The authors declare that no competing interests exist.
  7. Eli Eisenberg

    Sagol school of Neuroscience, Tel Aviv University, Tel Aviv, Israel
    For correspondence
    elieis@post.tau.ac.il
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animal experimentation was conducted in accordance to the guidelines of the Marine Biological Laboratory in Woods Hole, Massachusetts.

Reviewing Editor

  1. Roderic Guigó, Center for Genomic Regulation, Spain

Publication history

  1. Received: October 15, 2014
  2. Accepted: January 8, 2015
  3. Accepted Manuscript published: January 8, 2015 (version 1)
  4. Version of Record published: February 4, 2015 (version 2)

Copyright

© 2015, Alon et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 11,129
    Page views
  • 1,165
    Downloads
  • 62
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Genetics and Genomics
    Eilis Hannon et al.
    Research Article

    We performed a systematic analysis of blood DNA methylation profiles from 4,483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1,048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Michelle C Ward et al.
    Research Article Updated

    One life-threatening outcome of cardiovascular disease is myocardial infarction, where cardiomyocytes are deprived of oxygen. To study inter-individual differences in response to hypoxia, we established an in vitro model of induced pluripotent stem cell-derived cardiomyocytes from 15 individuals. We measured gene expression levels, chromatin accessibility, and methylation levels in four culturing conditions that correspond to normoxia, hypoxia, and short- or long-term re-oxygenation. We characterized thousands of gene regulatory changes as the cells transition between conditions. Using available genotypes, we identified 1,573 genes with a cis expression quantitative locus (eQTL) in at least one condition, as well as 367 dynamic eQTLs, which are classified as eQTLs in at least one, but not in all conditions. A subset of genes with dynamic eQTLs is associated with complex traits and disease. Our data demonstrate how dynamic genetic effects on gene expression, which are likely relevant for disease, can be uncovered under stress.