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Elife. 2017 Dec 27;6. pii: e32537. doi: 10.7554/eLife.32537.

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

Author information

1
Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States.
2
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle, United States.
3
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
4
Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, United States.
5
Center for Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle, United States.

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. We observed unexpectedly 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 the rate or accuracy of splicing.

KEYWORDS:

D. melanogaster; computational biology; genomics; kinetic investigations; mRNA splicing; mathematical modeling; systems biology

PMID:
29280736
PMCID:
PMC5762160
DOI:
10.7554/eLife.32537
[Indexed for MEDLINE]
Free PMC Article

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