Cryo-EM uncovers a sequential mechanism for RNA polymerase I pausing and stalling at abasic DNA lesions DOI
Alicia Santos-Aledo, Adrián Plaza-Pegueroles, Marta Sanz Murillo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract RNA polymerase I (Pol I) transcribes ribosomal DNA (rDNA) to produce the rRNA precursor, which accounts for up 60% of total transcriptional activity in growing cells. Pol monitors rDNA integrity and influences cell survival, but little is known about how this enzyme processes abasic lesions. Here, we report electron cryo-microscopy (cryo-EM) structures at different stages stalling sites, supported by vitro transcription studies. Our results show that templating sites can slow nucleotide addition base sandwiching between 3’-end bridge helix. However, presence a site induces opening cleft either dissociation from or access A12-Ct into active stimulate cleavage. Nucleotide opposite lesion an early translocation intermediate previously-described paused states, as bases hybrid tilt form hydrogen bonds with newly-added base. While state strongly disfavoured, intrinsic cleavage acts failsafe mechanism minimize bypass. uncover two-step leading persistent after Ap distinct arrest CPD lesions II blockage sites.

Язык: Английский

The PNUTS phosphatase complex controls transcription pause release DOI Creative Commons
Jessica R. Kelley, Emilia Dimitrova,

Maciej Maciuszek

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(24), С. 4843 - 4861.e8

Опубликована: Ноя. 26, 2024

Язык: Английский

Процитировано

7
The CDK9-SPT5 axis in control of transcription elongation by RNAPII DOI
Rui Sun, Robert P. Fisher

Journal of Molecular Biology, Год журнала: 2024, Номер unknown, С. 168746 - 168746

Опубликована: Авг. 1, 2024

Язык: Английский

Процитировано

6
RNA Polymerase II Activity Control of Gene Expression and Involvement in Disease DOI Creative Commons

James C. Kuldell,

Craig D. Kaplan

Journal of Molecular Biology, Год журнала: 2024, Номер 437(1), С. 168770 - 168770

Опубликована: Авг. 28, 2024

Gene expression is dependent on RNA Polymerase II (Pol II) activity in eukaryotes. In addition to determining the rate of synthesis for all protein coding genes, Pol serves as a platform recruitment factors and regulation co-transcriptional events, from processing chromatin modification remodeling. The transcriptome can be shaped by changes kinetics affecting itself or because alterations events that are responsive coupled with transcription. Genetic, biochemical, structural approaches model organisms have revealed critical insights into how works types regulate it. complexity generally increases organismal complexity. this review, we describe fundamental aspects shape gene expression, discuss recent advances elongation regulated altered function linked human disease aging.

Язык: Английский

Процитировано

4
Structural insights into promoter-proximal pausing of RNA polymerase II at +1 nucleosome DOI Creative Commons
Masahiro Naganuma, Tomoya Kujirai, Haruhiko Ehara

и другие.

Science Advances, Год журнала: 2025, Номер 11(10)

Опубликована: Март 5, 2025

The metazoan transcription elongation complex (EC) of RNA polymerase II (RNAPII) generally stalls between the start site and first (+1) nucleosome. This promoter-proximal pausing involves negative factor (NELF), 5,6-dichloro-1-β-d-ribobenzimidazole sensitivity-inducing (DSIF), IIS (TFIIS) is critical for subsequent productive elongation. However, detailed mechanism involvement +1 nucleosome remain enigmatic. Here, we report cryo-electron microscopy structures ECs stalled on nucleosomal DNA. In absence TFIIS, EC backtracked/arrested due to conflicts NELF We identified two alternative binding modes NELF, one which reveals a contact with downstream DNA through conserved NELF-E basic helix. Upon progressed establish paused partially unwrapped strongly restricts progression further downstream. These illuminate RNAPII pausing/stalling at

Язык: Английский

Процитировано

0
Regulation of RNA polymerase II transcription through re-initiation and bursting DOI
Michael Nagel, Dylan J. Taatjes

Molecular Cell, Год журнала: 2025, Номер 85(10), С. 1907 - 1919

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Evolution of promoter-proximal pausing enabled a new layer of transcription control DOI Creative Commons
Alexandra G. Chivu, Benjamin Basso, Abderhman Abuhashem

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Фев. 19, 2023

Abstract Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role in gene regulation, we do not understand evolutionary processes that led to emergence Pol or its transition rate-limiting actively controlled by transcription factors. Here analyzed species across tree life. Unicellular eukaryotes display slow acceleration near start sites transitioned longer-lived, focused pause metazoans. This event coincided with evolution new subunits NELF and 7SK complexes. Depletion mammals shifted promoter-proximal buildup from site into early body compromised transcriptional activation for set heat shock genes. Our work details history sheds light on how mechanisms evolve.

Язык: Английский

Процитировано

6
Pause Patrol: Negative Elongation Factor’s role in Promoter-Proximal Pausing and beyond DOI
Annette J. Diao,

Bonnie Su,

Seychelle M. Vos

и другие.

Journal of Molecular Biology, Год журнала: 2024, Номер unknown, С. 168779 - 168779

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

2
A trimeric USP11/USP7/TCEAL1 complex stabilizes RNAPII during early transcription to sustain oncogenic gene expression DOI Creative Commons

Markus Dehmer,

Peter Gallant,

Steffi Herold

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 30, 2024

Abstract During early transcription, RNA polymerase II (RNAPII) undergoes a series of structural transitions controlled by cyclin-dependent kinases. Whether protein ubiquitylation and proteasomal degradation affect the fate RNAPII close to promoters is less well understood. Here we show that deubiquitylating enzyme USP11 its heterodimeric partner USP7 form trimeric complex with TCEAL1, member poorly understood TCEAL (TCEA/TFIIS-like) family. TCEAL1 shares sequence homology interaction domain TCEA/TFIIS elongation factor, which controls backtracked RNAPII. stabilizes complexes recruited core when transcription blocked globally enhances chromatin association during transcription. Mechanistically, USP11/USP7/TCEAL1 competes TFIIS for binding protects RPB8, an essential subunit RNAPII, from degradation, likely preventing excessive TFIIS-mediated transcript cleavage disassembly. In neuroblastoma other tumors, TCEAL1-dependent genes define TGF beta-dependent gene expression program characteristic mesenchymal invasive tumor cell types, suggesting trimer support critical oncogenic (190 words).

Язык: Английский

Процитировано

1
Changing structures, changing paradigms: NELF helps regulate paused or elongating RNA polymerase II DOI Creative Commons
William F. Richter, Dylan J. Taatjes

Molecular Cell, Год журнала: 2024, Номер 84(7), С. 1180 - 1182

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

0
Cryo-EM uncovers a sequential mechanism for RNA polymerase I pausing and stalling at abasic DNA lesions DOI
Alicia Santos-Aledo, Adrián Plaza-Pegueroles, Marta Sanz Murillo

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract RNA polymerase I (Pol I) transcribes ribosomal DNA (rDNA) to produce the rRNA precursor, which accounts for up 60% of total transcriptional activity in growing cells. Pol monitors rDNA integrity and influences cell survival, but little is known about how this enzyme processes abasic lesions. Here, we report electron cryo-microscopy (cryo-EM) structures at different stages stalling sites, supported by vitro transcription studies. Our results show that templating sites can slow nucleotide addition base sandwiching between 3’-end bridge helix. However, presence a site induces opening cleft either dissociation from or access A12-Ct into active stimulate cleavage. Nucleotide opposite lesion an early translocation intermediate previously-described paused states, as bases hybrid tilt form hydrogen bonds with newly-added base. While state strongly disfavoured, intrinsic cleavage acts failsafe mechanism minimize bypass. uncover two-step leading persistent after Ap distinct arrest CPD lesions II blockage sites.

Язык: Английский

Процитировано

0