Eukaryotic genes must be condensed into chromatin while remaining accessible to the transcriptional machinery to support gene expression. Among the three eukaryotic RNA polymerases (RNAP), RNAPII is unique, partly because of the C-terminal domain (CTD) of its largest subunit, Rpb1. Rpb1 CTD can be extensively modified during the transcription cycle, allowing for the co-transcriptional recruitment of specific interacting proteins. These include chromatin remodeling factors that control the opening or closing of chromatin. How the CTD-less RNAPI and RNAPIII deal with chromatin at rRNA and tRNA genes is less understood. Here, we review recent advances in our understanding of how the chromatin at tRNA genes and rRNA genes can be remodeled in response to environmental cues in yeast, with a particular focus on the role of local RNAPII transcription in recruiting chromatin remodelers at these loci. In fission yeast, RNAPII transcription at tRNA genes is important to re-establish a chromatin environment permissive to tRNA transcription, which supports growth from stationary phase. In contrast, local RNAPII transcription at rRNA genes correlates with the closing of the chromatin in starvation in budding and fission yeast, suggesting a role in establishing silent chromatin. These opposite roles might support a general model where RNAPII transcription recruits chromatin remodelers to tRNA and rRNA genes to promote the closing and reopening of chromatin in response to the environment.
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http://dx.doi.org/10.1002/yea.3921 | DOI Listing |
Nat Commun
December 2024
Division of Experimental Parasitology, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, 82152, Planegg-Martinsried, Germany.
The eukaryotic nucleus exhibits a highly organized 3D genome architecture, with RNA transcription and processing confined to specific nuclear structures. While intra-chromosomal interactions, such as promoter-enhancer dynamics, are well-studied, the role of inter-chromosomal interactions remains poorly understood. Investigating these interactions in mammalian cells is challenging due to large genome sizes and the need for deep sequencing.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Biochemistry, Brandeis University, Waltham, MA 02453.
Transcription activators trigger transcript production by RNA Polymerase II (RNApII) via the Mediator coactivator complex. Here the dynamics of activator, Mediator, and RNApII binding at promoter DNA were analyzed using multi-wavelength single-molecule microscopy of fluorescently labeled proteins in budding yeast nuclear extract. Binding of Mediator and RNApII to the template required activator and an upstream activator sequence (UAS), but not a core promoter.
View Article and Find Full Text PDFTrends Cell Biol
December 2024
Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Electronic address:
Cellular homeostasis declines with age due to the declining fidelity of biosynthetic processes and the accumulation of molecular damage. Yet, it remains largely elusive how individual processes are affected during aging and what their specific contribution to age-related functional decline is. This review discusses a series of recent publications that has shown that transcription elongation is compromised during aging due to increasing DNA damage, stalling of RNA polymerase II (RNAPII), erroneous transcription initiation in gene bodies, and accelerated RNAPII elongation.
View Article and Find Full Text PDFFEBS Lett
December 2024
Department of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
The transcription-coupled repair (TCR) pathway resolves transcription-blocking DNA lesions to maintain cellular function and prevent transcriptional arrest. Stalled RNA polymerase II (RNAPII) triggers repair mechanisms, including RNAPII ubiquitination, which recruit UVSSA and TFIIH. Defects in TCR-associated genes cause disorders like Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and recently defined AMeDS.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Institute of Biochemistry, University of Kiel, Rudolf-Höber-Straße 1, Kiel 24118, Germany.
Transcripts produced by RNA polymerase II (RNAPII) are fundamental for cellular responses to environmental changes. It is therefore no surprise that there exist multiple avenues for the regulation of this process. To explore the regulation mediated by RNAPII-interacting proteins, we used a small interfering RNA (siRNA)-based screen to systematically evaluate their influence on RNA synthesis.
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