Free circular introns with an unusual branchpoint in neuronal projections

  1. Harleen Saini  Is a corresponding author
  2. Alicia A Bicknell
  3. Sean R Eddy  Is a corresponding author
  4. Melissa J Moore  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. Howard Hughes Medical Institute, Harvard University, United States

Abstract

The polarized structure of axons and dendrites in neuronal cells depends in part on RNA localization. Previous studies have looked at which polyadenylated RNAs are enriched in neuronal projections or at synapses, but less is known about the distribution of non-adenylated RNAs. By physically dissecting projections from cell bodies of primary rat hippocampal neurons and sequencing total RNA, we found an unexpected set of free circular introns with a non-canonical branchpoint enriched in neuronal projections. These introns appear to be tailless lariats that escape debranching. They lack ribosome occupancy, sequence conservation, and known localization signals, and their function, if any, is not known. Nonetheless, their enrichment in projections has important implications for our understanding of the mechanisms by which RNAs reach distal compartments of asymmetric cells.

Data availability

All raw data (fastq format) and corresponding coverage files (bigwig format) are available at NCBI GEO under accession number GSE129924, and a tarball of supplementary tables and code is at http://eddylab.org/publications.html#Saini19.

The following data sets were generated

Article and author information

Author details

  1. Harleen Saini

    RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    harleen.saini@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6954-4098
  2. Alicia A Bicknell

    RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sean R Eddy

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    For correspondence
    seaneddy@fas.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6676-4706
  4. Melissa J Moore

    RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    melissa.moore@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of General Medical Sciences (R01-GM53007)

  • Melissa J Moore

Howard Hughes Medical Institute

  • Sean R Eddy
  • Melissa J Moore

Howard Hughes Medical Institute (International Student Research Fellowship)

  • Harleen Saini

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animals were handled in accordance with protocols approved by the Institutional Animal Careand Use Committees at University of Massachusetts Medical School (docket #A-2245-16) and Harvard University (protocol #10-16-1). All surgery was performed after euthanization, and every effort was made to minimize suffering.

Reviewing Editor

  1. Benjamin J Blencowe, University of Toronto, Canada

Publication history

  1. Received: April 19, 2019
  2. Accepted: November 6, 2019
  3. Accepted Manuscript published: November 7, 2019 (version 1)
  4. Version of Record published: November 26, 2019 (version 2)

Copyright

© 2019, Saini 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.

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  1. Harleen Saini
  2. Alicia A Bicknell
  3. Sean R Eddy
  4. Melissa J Moore
(2019)
Free circular introns with an unusual branchpoint in neuronal projections
eLife 8:e47809.
https://doi.org/10.7554/eLife.47809

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