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

Pai, Athma A.; Henriques, Telmo; McCue, Kayla; Burkholder, Adam; Adelman, Karen; Burge, Christopher B.

doi:10.7554/elife.32537.001

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

Journal Article · Wed Dec 27 00:00:00 EST 2017 · eLife

DOI:https://doi.org/10.7554/elife.32537.001· OSTI ID:1512506

Pai, Athma A. ^[1]; Henriques, Telmo ^[2]; McCue, Kayla ^[3]; Burkholder, Adam ^[4]; Adelman, Karen ^[2]; Burge, Christopher B. ^[3]

Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); None
National Inst. of Environmental Health Sciences, Research Triangle, NC (United States); Harvard Medical School, Boston, MA (United States)
Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
National Inst. of Environmental Health Sciences, Research Triangle, NC (United States)

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. Here, 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.