Spt5 orchestrates cryptic transcript suppression and transcriptional directionality.


Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
22 Oct 2024
Historique:
received: 11 06 2024
accepted: 03 10 2024
medline: 23 10 2024
pubmed: 23 10 2024
entrez: 22 10 2024
Statut: epublish

Résumé

Spt5 is a well-conserved factor that manipulates multiple stages of transcription from promoter-proximal pausing (PPP) to termination. Recent studies have revealed an unexpected increase of antisense transcripts near promoters in cells expressing mutant Spt5. Here, we identify Spt5p-restricted intragenic antisense transcripts and their close relationship with sense transcription in yeast. We confirm that Spt5 CTR phosphorylation is also important to retain Spt5's facility to regulate antisense transcription. The genes whose antisense transcription is strongly suppressed by Spt5p share strong endogenous sense transcription and weak antisense transcription, and this pattern is conserved in humans. Mechanistically, we found that Spt5p depletion increased histone acetylation to initiate intragenic antisense transcription by altering chromatin structure. We additionally identified termination factors that appear to be involved in the ability of Spt5p to restrict antisense transcription. By unveiling a new role of Spt5 in finely balancing the bidirectionality of transcription, we demonstrate that Spt5-mediated suppression of DSIF complex regulated-unstable transcripts (DUTs) is essential to sustain the accurate transcription by RNA polymerase II.

Identifiants

pubmed: 39438667
doi: 10.1038/s42003-024-07014-7
pii: 10.1038/s42003-024-07014-7
doi:

Substances chimiques

Transcriptional Elongation Factors 0
SPT5 transcriptional elongation factor 138673-72-0
Saccharomyces cerevisiae Proteins 0
Chromosomal Proteins, Non-Histone 0
RNA Polymerase II EC 2.7.7.-
RNA, Antisense 0
Histones 0
Chromatin 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1370

Informations de copyright

© 2024. The Author(s).

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Auteurs

Haejin An (H)

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

Hyeokjun Yang (H)

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

Daeyoup Lee (D)

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. daeyoup@kaist.ac.kr.

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