The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture
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 leng...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/32537 |
| _version_ | 1818027059435274240 |
|---|---|
| author | Athma A Pai Telmo Henriques Kayla McCue Adam Burkholder Karen Adelman Christopher B Burge |
| author_facet | Athma A Pai Telmo Henriques Kayla McCue Adam Burkholder Karen Adelman Christopher B Burge |
| author_sort | Athma A Pai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T04:41:53Z |
| format | Article |
| id | doaj.art-68b7f83da5c24e6d8e8a964d15ff0e17 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:41:53Z |
| publishDate | 2017-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-68b7f83da5c24e6d8e8a964d15ff0e172022-12-22T02:01:52ZengeLife Sciences Publications LtdeLife2050-084X2017-12-01610.7554/eLife.32537The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architectureAthma A Pai0https://orcid.org/0000-0002-7995-9948Telmo Henriques1Kayla McCue2Adam Burkholder3Karen Adelman4https://orcid.org/0000-0001-5364-334XChristopher B Burge5https://orcid.org/0000-0001-9047-5648Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, United StatesEpigenetics 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 StatesProgram in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, United StatesCenter for Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle, United StatesEpigenetics 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 StatesDepartments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, United StatesProduction 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.https://elifesciences.org/articles/32537mRNA splicingkinetic investigationsmathematical modelinggenomics |
| spellingShingle | Athma A Pai Telmo Henriques Kayla McCue Adam Burkholder Karen Adelman Christopher B Burge The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture eLife mRNA splicing kinetic investigations mathematical modeling genomics |
| title | The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture |
| title_full | The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture |
| title_fullStr | The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture |
| title_full_unstemmed | The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture |
| title_short | The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture |
| title_sort | kinetics of pre mrna splicing in the drosophila genome and the influence of gene architecture |
| topic | mRNA splicing kinetic investigations mathematical modeling genomics |
| url | https://elifesciences.org/articles/32537 |
| work_keys_str_mv | AT athmaapai thekineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT telmohenriques thekineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT kaylamccue thekineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT adamburkholder thekineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT karenadelman thekineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT christopherbburge thekineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT athmaapai kineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT telmohenriques kineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT kaylamccue kineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT adamburkholder kineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT karenadelman kineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture AT christopherbburge kineticsofpremrnasplicinginthedrosophilagenomeandtheinfluenceofgenearchitecture |