Hochschulschrift

Sites of transcription initiation drive mRNA isoform selection

Abstract: 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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Cell. - 186, 11 (2023) , 2438-2455.e22, ISSN: 1097-4172

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2024
Creator
Alfonso-Gonzalez, Carlos
Legnini, Ivano
Holec, Sarah
Arrigoni, Laura
Ozbulut, Hasan Can
Mateos, Fernando
Koppstein, David
Rybak-Wolf, Agnieszka
Bönisch, Ulrike
Rajewsky, Nikolaus
Hilgers, Valérie

DOI
10.1016/j.cell.2023.04.012
URN
urn:nbn:de:bsz:25-freidok-2458987
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:51 PM CET

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Object type

  • Hochschulschrift

Associated

Time of origin

  • 2024

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