BEND3 represses rDNA transcription by stabilizing a NoRC component via USP21 deubiquitinase
A. Ali Khan,Sumanprava Giri,Yating Wang,Arindam Chakraborty,Archit K. Ghosh,Aparna Anantharaman,Vasudha Aggarwal,Kizhakke Mattada Sathyan,Taekjip Ha,Kannanganattu V. Prasanth,Supriya G. Prasanth +10 more
TLDR
It is demonstrated in mammalian cells that BANP, E5R, and Nac1 (BEN) domain 3 (BEND3), a quadruple BEN domain-containing protein, localizes in nucleoli and binds to ribosomal RNA gene promoters to help repress rRNA genes.Abstract:
Ribosome biogenesis dictates the translational capacity of cells. Several mechanisms establish and maintain transcriptional output from eukaryotic ribosomal DNA (rDNA) loci. rDNA silencing is one such mechanism that ensures the inactivity and hence the maintenance of a silenced state of a subset of rRNA gene copies. Whereas oncogenic agents stimulate rRNA gene transcription, tumor suppressors decrease rRNA gene transcription. We demonstrate in mammalian cells that BANP, E5R, and Nac1 (BEN) domain 3 (BEND3), a quadruple BEN domain-containing protein, localizes in nucleoli and binds to ribosomal RNA gene promoters to help repress rRNA genes. Loss of BEND3 increases histone H3K4 trimethylation and, correspondingly, decreases rDNA promoter DNA methylation, consistent with a role for BEND3 in rDNA silencing. BEND3 associates with the nucleolar-remodeling complex (NoRC), and SUMOylated BEND3 stabilizes NoRC component TTF-1–interacting protein 5 via association with ubiquitin specific protease 21 (USP21) debiquitinase. Our results provide mechanistic insights into how the novel rDNA transcription repressor BEND3 acts together with NoRC to actively coordinate the establishment of rDNA silencing.read more
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Posttranslational mutagenesis: A chemical strategy for exploring protein side-chain diversity
Tom H. Wright,Ben J. Bower,Justin M. Chalker,Gonçalo J. L. Bernardes,Rafal P. Wiewiora,Wai-Lung Ng,Ritu Raj,Sarah Faulkner,M. Robert J. Vallée,Anuchit Phanumartwiwath,Oliver D. Coleman,Marie-Laëtitia Thézénas,Maola Khan,Sébastien R. G. Galan,Lukas Lercher,Matthew W. Schombs,Stefanie Gerstberger,Maria E. Palm-Espling,Andrew Baldwin,Benedikt M. Kessler,Timothy D. W. Claridge,Shabaz Mohammed,Benjamin G. Davis +22 more
TL;DR: This work reasoned that mild, carbon-centered free radical chemistry would be enabled by matching free-radical reactivity with a suitable, uniquely reactive functional group partner that possesses a chemical affinity for such singly occupied molecular orbitals.
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Non-coding RNA and chromatin remodeling: intergenic transcripts regulate the epigenetic state of rRNA genes
TL;DR: It is shown that IGS transcripts are required for establishing and maintaining a specific heterochromatic configuration at the promoter of a subset of rDNA arrays.
Journal ArticleDOI
The Epigenetic Pathways to Ribosomal DNA Silencing
TL;DR: This work focuses on recent advances in the epigenetic regulation of rDNA silencing in Saccharomyces cerevisiae and in mammals, including regulation by several histone modifications and several protein components associated with the inner nuclear membrane within the nucleolus.
Journal ArticleDOI
DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets.
TL;DR: Recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer are described.
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Ancient Gene Capture and Recent Gene Loss Shape the Evolution of Orthopoxvirus-Host Interaction Genes.
TL;DR: In this article, the authors identified the ORPV accessory genes and reconstructed the history of their gain and loss during the evolution of ORPVs from chordopoxviruses.
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