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

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· OSTI ID:1414969

^[1]; Henriques, Telmo ^[2]; McCue, Kayla ^[3]; Burkholder, Adam ^[4]; ^[2]; ^[5]

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

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Research Organization:: Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: FG02-97ER25308

OSTI ID:: 1414969

Alternate ID(s):: OSTI ID: 1414970
OSTI ID: 1629792

Journal Information:: eLife, Journal Name: eLife Vol. 6; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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