The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture

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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.

Data availability

The following data sets were generated

1. Pai AA
2. Henriques T
3. McCue K
4. Burkholder A
5. Adelman K
6. Burge CB
(2017) Drosophila S2 cell 4sU RNA-seq data
Gene Expression Omnibus (GEO) accession GSE93763.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi

Article and author information

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Athma A Pai

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-7995-9948
Telmo Henriques

Epigenetics and Stem Cell Biology Laboratory, National Institute for Environmental Health Sciences, Durham, United States

Competing interests
No competing interests declared.
Kayla McCue

Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, United States

Competing interests
No competing interests declared.
Adam Burkholder

Center for Integrative Bioinformatics, National Institute for Environmental Health Sciences, Durham, United States

Competing interests
No competing interests declared.
Karen Adelman

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States

Competing interests
Karen Adelman, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-5364-334X
Christopher B Burge

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

For correspondence
cburge@mit.edu

Competing interests
No competing interests declared.

"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.

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.