title: TFIIS is required for the balanced expression of the genes encoding ribosomal components under transcriptional stress.
abstract: Transcription factor IIS (TFIIS) stimulates RNA cleavage by RNA polymerase II by allowing backtracked enzymes to resume transcription elongation. Yeast cells do not require TFIIS for viability, unless they suffer severe transcriptional stress due to NTP-depleting drugs like 6-azauracil or mycophenolic acid. In order to broaden our knowledge on the role of TFIIS under transcriptional stress, we carried out a genetic screening for suppressors of TFIIS-lacking cells' sensitivity to 6-azauracil and mycophenolic acid. Five suppressors were identified, four of which were related to the transcriptional regulation of those genes encoding ribosomal components [rRNAs and ribosomal proteins (RP)], including global regulator SFP1. This led us to discover that RNA polymerase II is hypersensitive to the absence of TFIIS under NTP scarcity conditions when transcribing RP genes. The absence of Sfp1 led to a profound alteration of the transcriptional response to NTP-depletion, thus allowing the expression of RP genes to resist these stressful conditions in the absence of TFIIS. We discuss the effect of transcriptional stress on ribosome biogenesis and propose that TFIIS contributes to prevent a transcriptional imbalance between rDNA and RP genes.
authors.affiliation: Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Avda Reina Mercedes 6. E-41012 Seville, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez-Herreros
authors.forename: Lola
authors.initials: L
authors.lastname: de Miguel-Jiménez
authors.forename: Macarena
authors.initials: M
authors.lastname: Morillo-Huesca
authors.forename: Lidia
authors.initials: L
authors.lastname: Delgado-Ramos
authors.forename: María C
authors.initials: MC
authors.lastname: Muñoz-Centeno
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
mesh_terms: D004275:DNA, Ribosomal / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D009154:Mutation; D009173:Mycophenolic Acid / Q000494:pharmacology; D012319:RNA Polymerase II / Q000378:metabolism; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics*; D013489:Suppression, Genetic; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism / Q000502:physiology*; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C068394:DST1 protein, S cerevisiae; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; C117421:SFP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D014498:Uracil; D012319:RNA Polymerase II; D009173:Mycophenolic Acid; C100248:azauracil