Global donor and acceptor splicing site kinetics in human cells.
RNA metabolism
co-transcriptional splicing
computational biology
gene regulatory elements
genetics
genomics
human
metabolic labeling
splicing kinetic
splicing yield
systems biology
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
26 04 2019
26 04 2019
Historique:
received:
20
01
2019
accepted:
25
04
2019
pubmed:
27
4
2019
medline:
25
2
2020
entrez:
27
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31025937
doi: 10.7554/eLife.45056
pii: 45056
pmc: PMC6548502
doi:
pii:
Banques de données
GEO
['GSE129635', 'GSE75792', 'GSE53328']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Molecular Biology Organization
ID : ALTF-1261-2014
Pays : International
Organisme : Horizon 2020
ID : SOUND 633974
Pays : International
Organisme : Horizon 2020 SOUND
ID : 633974
Pays : International
Informations de copyright
© 2019, Wachutka et al.
Déclaration de conflit d'intérêts
LW, LC, JG, PC No competing interests declared
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