Global donor and acceptor splicing site kinetics in human cells
© 2019, Wachutka et al..
RNA splicing is an essential part of eukaryotic gene expression. Although the mechanism of splicing has been extensively studied in vitro, in vivo kinetics for the two-step splicing reaction remain poorly understood. Here, we combine transient transcriptome sequencing (TT-seq) and mathematical modeling to quantify RNA metabolic rates at donor and acceptor splice sites across the human genome. Splicing occurs in the range of minutes and is limited by the speed of RNA polymerase elongation. Splicing kinetics strongly depends on the position and nature of nucleotides flanking splice sites, and on structural interactions between unspliced RNA and small nuclear RNAs in spliceosomal intermediates. Finally, we introduce the 'yield' of splicing as the efficiency of converting unspliced to spliced RNA and show that it is highest for mRNAs and independent of splicing kinetics. These results lead to quantitative models describing how splicing rates and yield are encoded in the human genome.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
eLife - 8(2019) vom: 26. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wachutka, Leonhard [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.02.2020 Date Revised 09.01.2021 published: Electronic GEO: GSE129635, GSE75792, GSE53328 Citation Status MEDLINE |
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| doi: |
10.7554/eLife.45056 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM296459313 |
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| 245 | 1 | 0 | |a Global donor and acceptor splicing site kinetics in human cells |
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| 500 | |a GEO: GSE129635, GSE75792, GSE53328 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019, Wachutka et al. | ||
| 520 | |a RNA splicing is an essential part of eukaryotic gene expression. Although the mechanism of splicing has been extensively studied in vitro, in vivo kinetics for the two-step splicing reaction remain poorly understood. Here, we combine transient transcriptome sequencing (TT-seq) and mathematical modeling to quantify RNA metabolic rates at donor and acceptor splice sites across the human genome. Splicing occurs in the range of minutes and is limited by the speed of RNA polymerase elongation. Splicing kinetics strongly depends on the position and nature of nucleotides flanking splice sites, and on structural interactions between unspliced RNA and small nuclear RNAs in spliceosomal intermediates. Finally, we introduce the 'yield' of splicing as the efficiency of converting unspliced to spliced RNA and show that it is highest for mRNAs and independent of splicing kinetics. These results lead to quantitative models describing how splicing rates and yield are encoded in the human genome | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a RNA metabolism | |
| 650 | 4 | |a co-transcriptional splicing | |
| 650 | 4 | |a computational biology | |
| 650 | 4 | |a gene regulatory elements | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a human | |
| 650 | 4 | |a metabolic labeling | |
| 650 | 4 | |a splicing kinetic | |
| 650 | 4 | |a splicing yield | |
| 650 | 4 | |a systems biology | |
| 700 | 1 | |a Caizzi, Livia |e verfasserin |4 aut | |
| 700 | 1 | |a Gagneur, Julien |e verfasserin |4 aut | |
| 700 | 1 | |a Cramer, Patrick |e verfasserin |4 aut | |
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