Sites of transcription initiation drive mRNA isoform selection.
5ʹ-3ʹ coupling
Drosophila
alternative polyadenylation
human brain organoids
long-read sequencing
mRNA isoform
nervous system
p300/CBP
transcription
transcription start site
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
25 05 2023
25 05 2023
Historique:
received:
25
05
2022
revised:
16
12
2022
accepted:
06
04
2023
medline:
29
5
2023
pubmed:
14
5
2023
entrez:
13
5
2023
Statut:
ppublish
Résumé
The generation of distinct messenger RNA isoforms through alternative RNA processing modulates the expression and function of genes, often in a cell-type-specific manner. Here, we assess the regulatory relationships between transcription initiation, alternative splicing, and 3' end site selection. Applying long-read sequencing to accurately represent even the longest transcripts from end to end, we quantify mRNA isoforms in Drosophila tissues, including the transcriptionally complex nervous system. We find that in Drosophila heads, as well as in human cerebral organoids, 3' end site choice is globally influenced by the site of transcription initiation (TSS). "Dominant promoters," characterized by specific epigenetic signatures including p300/CBP binding, impose a transcriptional constraint to define splice and polyadenylation variants. In vivo deletion or overexpression of dominant promoters as well as p300/CBP loss disrupted the 3' end expression landscape. Our study demonstrates the crucial impact of TSS choice on the regulation of transcript diversity and tissue identity.
Identifiants
pubmed: 37178687
pii: S0092-8674(23)00408-7
doi: 10.1016/j.cell.2023.04.012
pmc: PMC10228280
pii:
doi:
Substances chimiques
RNA Isoforms
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2438-2455.e22Subventions
Organisme : NIH HHS
ID : P40 OD018537
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM084947
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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