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Title: The ribosome assembly gene network is controlled by the feedback regulation of transcription elongation.
Authors: Gómez-Herreros, Fernando
Margaritis, Thanasis
Rodríguez-Galán, Olga
Pelechano, Vicent
Begley, Victoria
Millán-Zambrano, Gonzalo
Morillo-Huesca, Macarena
Muñoz-Centeno, Mari Cruz
Pérez-Ortín, José E
de la Cruz, Jesús
Holstege, Frank C P
Chávez, Sebastián
metadata.dc.subject.mesh: ATP-Binding Cassette Transporters
Adenosine Triphosphatases
Feedback, Physiological
Gene Regulatory Networks
Histone Chaperones
Organelle Biogenesis
RNA Processing, Post-Transcriptional
RNA, Ribosomal
Ribosomal Proteins
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Synthetic Lethal Mutations
Transcription Elongation, Genetic
Transcriptional Elongation Factors
Issue Date: 2017
Abstract: Ribosome assembly requires the concerted expression of hundreds of genes, which are transcribed by all three nuclear RNA polymerases. Transcription elongation involves dynamic interactions between RNA polymerases and chromatin. We performed a synthetic lethal screening in Saccharomyces cerevisiae with a conditional allele of SPT6, which encodes one of the factors that facilitates this process. Some of these synthetic mutants corresponded to factors that facilitate pre-rRNA processing and ribosome biogenesis. We found that the in vivo depletion of one of these factors, Arb1, activated transcription elongation in the set of genes involved directly in ribosome assembly. Under these depletion conditions, Spt6 was physically targeted to the up-regulated genes, where it helped maintain their chromatin integrity and the synthesis of properly stable mRNAs. The mRNA profiles of a large set of ribosome biogenesis mutants confirmed the existence of a feedback regulatory network among ribosome assembly genes. The transcriptional response in this network depended on both the specific malfunction and the role of the regulated gene. In accordance with our screening, Spt6 positively contributed to the optimal operation of this global network. On the whole, this work uncovers a feedback control of ribosome biogenesis by fine-tuning transcription elongation in ribosome assembly factor-coding genes.
metadata.dc.identifier.doi: 10.1093/nar/gkx529
Appears in Collections:Producción 2020

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