Mechanisms of lncRNA biogenesis as revealed by nascent transcriptomics

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(6), P. 389 - 406

Published: Jan. 25, 2022

Language: Английский

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H3K4me3 regulates RNA polymerase II promoter-proximal pause-release

Nature, Journal Year: 2023, Volume and Issue: 615(7951), P. 339 - 348

Published: March 1, 2023

Abstract Trimethylation of histone H3 lysine 4 (H3K4me3) is associated with transcriptional start sites and has been proposed to regulate transcription initiation 1,2 . However, redundant functions the H3K4 SET1/COMPASS methyltransferase complexes complicate elucidation specific role H3K4me3 in regulation 3,4 Here, using mouse embryonic stem cells as a model system, we show that acute ablation shared subunits leads complete loss all methylation. Turnover occurs more rapidly than H3K4me1 H3K4me2 dependent on KDM5 demethylases. Notably, does not have detectable effects but widespread decrease output, an increase RNA polymerase II (RNAPII) pausing slower elongation. We required for recruitment integrator complex subunit 11 (INTS11), which essential eviction paused RNAPII Thus, our study demonstrates distinct pause-release elongation rather initiation.

Language: Английский

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Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT

Science, Journal Year: 2022, Volume and Issue: 377(6611)

Published: Aug. 18, 2022

During gene transcription, RNA polymerase II (RNAPII) traverses nucleosomes in chromatin, but the mechanism has remained elusive. Using cryo–electron microscopy, we obtained structures of RNAPII elongation complex (EC) passing through a nucleosome presence transcription factors Spt6, Spn1, Elf1, Spt4/5, and Paf1C histone chaperone FACT (facilitates chromatin transcription). The show snapshots EC progression on DNA mediating downstream disassembly, followed by its reassembly upstream EC, which is facilitated FACT. dynamically adapts to successively occurring subnucleosome intermediates, forming an interface with EC. form “cradle” at DNA-exit site support reassembly. These explain while maintaining structure epigenetic information.

Language: Английский

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Integrator endonuclease drives promoter-proximal termination at all RNA polymerase II-transcribed loci

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(22), P. 4232 - 4245.e11

Published: Oct. 28, 2022

Language: Английский

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Knowing when to stop: Transcription termination on protein-coding genes by eukaryotic RNAPII

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(3), P. 404 - 415

Published: Jan. 11, 2023

Gene expression is controlled in a dynamic and regulated manner to allow for the consistent steady of some proteins as well rapidly changing production other proteins. Transcription initiation has been major focus study because it highly regulated. However, termination transcription also plays an important role controlling gene expression. on protein-coding genes intimately linked with 3' end cleavage polyadenylation transcripts, generally results mature mRNA that exported from nucleus. Termination many non-coding can result transcript. dynamically regulated-premature readthrough occur response number cellular signals, these have varied consequences Here, we review eukaryotic by RNA polymerase II (RNAPII), focusing genes.

Language: Английский

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U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(8), P. 1264 - 1279.e10

Published: March 24, 2023

Language: Английский

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SPT5 stabilization of promoter-proximal RNA polymerase II

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(21), P. 4413 - 4424.e5

Published: Sept. 3, 2021

Language: Английский

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SPT6 functions in transcriptional pause/release via PAF1C recruitment

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(18), P. 3412 - 3423.e5

Published: Aug. 9, 2022

Language: Английский

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Structure of a backtracked hexasomal intermediate of nucleosome transcription

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(17), P. 3126 - 3134.e7

Published: July 19, 2022

Language: Английский

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Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1

Science Advances, Journal Year: 2022, Volume and Issue: 8(13)

Published: April 1, 2022

Pleiotropic transcription regulator RNA polymerase II (Pol II)–associated factor 1 (PAF1) governs multiple transcriptional steps and the deposition of several epigenetic marks. However, it remains unclear how ultimate outcome is determined by PAF1 whether relates to PAF1-controlled We use rapid degradation systems reveal direct functions in governing pausing partially recruiting Integrator-PP2A (INTAC), addition ensuring elongation. Following acute degradation, most destabilized undergoes effective release, which presumably relies on skewed balance between INTAC P-TEFb, resulting hyperphosphorylated substrates including SPT5. Impaired Pol progression during elongation, along with altered pause release frequency, determines final outputs. Moreover, causes a cumulative decline histone modifications. These alterations chromatin likely further influence production transcripts from target genes.

Language: Английский

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