Differential 3' processing of specific transcripts expands regulatory and protein diversity across neuronal cell types

  1. Saša Jereb
  2. Hun-Way Hwang
  3. Eric Van Otterloo
  4. Eve-Ellen Govek
  5. John J Fak
  6. Yuan Yuan
  7. Mary E Hatten
  8. Robert B Darnell  Is a corresponding author
  1. The Rockefeller University, United States
  2. University of Colorado, United States

Abstract

Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3'UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3'UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3'TR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies.

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The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Saša Jereb

    Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6862-4475
  2. Hun-Way Hwang

    Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eric Van Otterloo

    Department of Craniofacial Biology, University of Colorado, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eve-Ellen Govek

    Laboratory of Developmental Neurobiology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. John J Fak

    Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Yuan Yuan

    Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2718-8301
  7. Mary E Hatten

    Laboratory of Developmental Neurobiology, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9059-660X
  8. Robert B Darnell

    Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, United States
    For correspondence
    darnelr@rockefeller.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5134-8088

Funding

National Institutes of Health (NS034389)

  • Robert B Darnell

Howard Hughes Medical Institute

  • Robert B Darnell

Simons Foundation (SFARI 240432)

  • Robert B Darnell

National Institute of Dental and Craniofacial Research (K99DE026823)

  • Eric Van Otterloo

National Institutes of Health (NS081706)

  • Robert B Darnell

National Institutes of Health (NS097404)

  • Robert B Darnell

National Institutes of Health (1UM1HG008901)

  • Robert B Darnell

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

Ethics

Animal experimentation: Animals were maintained in an AAALAC-approved animal facility and all procedures were performed in accordance with IACUC guidelines (protocol number 17013).

Reviewing Editor

  1. Bin Tian, Rutgers University New Jersey Medical School, United States

Publication history

  1. Received: December 12, 2017
  2. Accepted: March 20, 2018
  3. Accepted Manuscript published: March 26, 2018 (version 1)
  4. Version of Record published: April 13, 2018 (version 2)

Copyright

© 2018, Jereb 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. Saša Jereb
  2. Hun-Way Hwang
  3. Eric Van Otterloo
  4. Eve-Ellen Govek
  5. John J Fak
  6. Yuan Yuan
  7. Mary E Hatten
  8. Robert B Darnell
(2018)
Differential 3' processing of specific transcripts expands regulatory and protein diversity across neuronal cell types
eLife 7:e34042.
https://doi.org/10.7554/eLife.34042

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