Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing.
CoLa-seq
GC content
U2AF
branch point
co-transcriptional splicing
exon definition
intron definition
lariat RNAs
modeling
polypyrimidine tract
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
15 12 2022
15 12 2022
Historique:
received:
09
12
2021
revised:
10
09
2022
accepted:
02
11
2022
pmc-release:
15
12
2023
pubmed:
27
11
2022
medline:
21
12
2022
entrez:
26
11
2022
Statut:
ppublish
Résumé
Long introns with short exons in vertebrate genes are thought to require spliceosome assembly across exons (exon definition), rather than introns, thereby requiring transcription of an exon to splice an upstream intron. Here, we developed CoLa-seq (co-transcriptional lariat sequencing) to investigate the timing and determinants of co-transcriptional splicing genome wide. Unexpectedly, 90% of all introns, including long introns, can splice before transcription of a downstream exon, indicating that exon definition is not obligatory for most human introns. Still, splicing timing varies dramatically across introns, and various genetic elements determine this variation. Strong U2AF2 binding to the polypyrimidine tract predicts early splicing, explaining exon definition-independent splicing. Together, our findings question the essentiality of exon definition and reveal features beyond intron and exon length that are determinative for splicing timing.
Identifiants
pubmed: 36435176
pii: S1097-2765(22)01066-8
doi: 10.1016/j.molcel.2022.11.004
pmc: PMC10448999
mid: NIHMS1854138
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4681-4699.e8Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM062264
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115945
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG011067
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM145373
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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