1. Computational and Systems Biology
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The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture

  1. Athma A Pai
  2. Telmo Henriques
  3. Kayla McCue
  4. Adam Burkholder
  5. Karen Adelman
  6. Christopher B Burge  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. National Institute for Environmental Health Sciences, United States
  3. Harvard Medical School, United States
Research Article
  • Cited 9
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Cite this article as: eLife 2017;6:e32537 doi: 10.7554/eLife.32537

Abstract

Production of most eukaryotic mRNAs requires splicing of introns from pre-mRNA. The splicing reaction requires definition of splice sites, which are initially recognized in either intron-spanning ('intron definition') or exon-spanning ('exon definition') pairs. To understand how exon and intron length and splice site recognition mode impact splicing, we measured splicing rates genome-wide in Drosophila, using metabolic labeling/RNA sequencing and new mathematical models to estimate rates. We found that the modal intron length range of 60-70 nt represents a local maximum of splicing rates, but that much longer exon-defined introns are spliced even faster and more accurately. Surprisingly, we observed low variation in splicing rates across introns in the same gene, suggesting the presence of gene-level influences, and we identified multiple gene level variables associated with splicing rate. Together our data suggest that developmental and stress response genes may have preferentially evolved exon definition in order to enhance rates of splicing.

Article and author information

Author details

  1. Athma A Pai

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7995-9948
  2. Telmo Henriques

    Epigenetics and Stem Cell Biology Laboratory, National Institute for Environmental Health Sciences, Durham, United States
    Competing interests
    No competing interests declared.
  3. Kayla McCue

    Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Adam Burkholder

    Center for Integrative Bioinformatics, National Institute for Environmental Health Sciences, Durham, United States
    Competing interests
    No competing interests declared.
  5. Karen Adelman

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    Karen Adelman, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5364-334X
  6. Christopher B Burge

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    cburge@mit.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9047-5648

Funding

National Institutes of Health (Z01-ES101987)

  • Telmo Henriques
  • Adam Burkholder
  • Karen Adelman

National Institutes of Health (R01-GM085319)

  • Athma A Pai
  • Christopher B Burge

Jane Coffin Childs Memorial Fund for Medical Research

  • Athma A Pai

U.S. Department of Energy (FG02-97ER25308)

  • Kayla McCue

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

Reviewing Editor

  1. Timothy W Nilsen, Case Western Reserve University, United States

Publication history

  1. Received: October 5, 2017
  2. Accepted: December 22, 2017
  3. Accepted Manuscript published: December 27, 2017 (version 1)
  4. Version of Record published: January 10, 2018 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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