Regulation of transcription elongation anticipates alternative gene expression strategies across the cell cycle

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

ABSTRACT Increasing evidence supports that the activity of RNA polymerase II (RNA pol II) during transcription elongation can be regulated to control rates. Using genomic run-on (GRO) and chromatin immunoprecipitation (RPCC), we have respectively measured active total present in body genes at 3 different stages mitotic cell cycle Saccharomyces cerevisiae : G1, S G2/M. Comparison values these three points defined patterns across cycle. Previously characterized cycling were found associated some patterns. A cluster with very divergent GRO RPCC was significantly enriched functionally related ribosome biogenesis (RiBi) structural components ribosome. We confirmed RiBi mRNA expression upregulates after START but decreases mitosis. Finally, analysed contribution stability each concerted decay is needed fully understand alternative strategies gene

Language: Английский

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SPT5 regulates RNA polymerase II stability via Cullin 3–ARMC5 recognition

Science Advances, Journal Year: 2025, Volume and Issue: 11(4)

Published: Jan. 24, 2025

The stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control gene expression. Our recent studies revealed that promoter-proximal Pol destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss transcription factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound as a substrate. Using an unbiased proteomic screening approach, identify armadillo repeat-containing 5 (ARMC5) adaptor required VCP/p97-dependent degradation SPT5-depleted, II. Genome-wide analyses indicate ARMC5 targets in BTB domain–dependent manner. Further biochemical analysis demonstrates interaction between and requires cyclin-dependent kinase 9 (CDK9), supporting phospho-dependent model. We propose defective, lacks SPT5 rapidly eliminated from chromatin noncanonical early termination pathway CDK9-dependent with CUL3-ARMC5 complex.

Language: Английский

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Post‐Transcriptional Regulation of Gene Expression and the Intricate Life of Eukaryotic mRNAs

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2025, Volume and Issue: 16(2)

Published: March 1, 2025

In recent years, there has been a growing appreciation for how regulatory events that occur either co- or post-transcriptionally contribute to the control of gene expression. Messenger RNAs (mRNAs) are extensively regulated throughout their metabolism in precise spatiotemporal manner requires sophisticated molecular mechanisms cell-type-specific expression, which dictates cell function. Moreover, dysfunction at any these steps can result variety human diseases, including cancers, muscular atrophies, and neurological diseases. This review summarizes central dogma biology, focusing on post-transcriptional regulation

Language: Английский

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Tripartite phosphorylation of SPT5 by CDK9 times pause release and tunes elongation rate of RNA polymerase II

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Regulation of transcription elongation anticipates alternative gene expression strategies across the cell cycle

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(5), P. e0317650 - e0317650

Published: May 7, 2025

A growing body of evidence supports the idea that RNA polymerase II (RNAP II) activity during transcription elongation can be regulated to control rates. Using genomic run-on and RNAP chromatin immunoprecipitation, we measured both active total across bodies genes at three different stages mitotic cell cycle in Saccharomyces cerevisiae : G1, S, G2/M. Comparison levels these revealed distinct patterns throughout cycle. Previously characterized cycling were associated with some patterns. cluster highly divergent immunoprecipitation was notably enriched related ribosome biogenesis structural components ribosome. We confirmed expression mRNAs increases after G1 but decreases following mitosis. Finally, analyzed contribution mRNA stability each found a coordinated regulation decay is necessary fully understand alternative strategies gene

Language: Английский

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Controlling Transcription Elongation and Termination: More Than a Means to An End

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: unknown, P. 168886 - 168886

Published: Nov. 1, 2024

Language: Английский

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