RESUMEN
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.
Asunto(s)
Proteínas Ribosómicas/biosíntesis , Estrés Fisiológico/genética , Transcripción Genética , Factores de Elongación Transcripcional/fisiología , ADN Ribosómico/metabolismo , Proteínas de Unión al ADN/genética , Mutación , Ácido Micofenólico/farmacología , ARN Polimerasa II/metabolismo , ARN Ribosómico/biosíntesis , Proteínas Ribosómicas/genética , Proteínas de Saccharomyces cerevisiae/genética , Supresión Genética , Factores de Elongación Transcripcional/metabolismo , Uracilo/análogos & derivados , Uracilo/farmacologíaRESUMEN
Cells vary in volume throughout their life cycle and in many other circumstances, while their genome remains identical. Hence, the RNA production factory must adapt to changing needs, while maintaining the same production lines. This paradox is resolved by different mechanisms in distinct cells and circumstances. RNA polymerases have evolved to cope with the particular circumstances of each case and the different characteristics of the several RNA molecule types, especially their stabilities. Here we review current knowledge on these issues. We focus on the yeast Saccharomyces cerevisiae, where many of the studies have been performed, although we compare and discuss the results obtained in other eukaryotes and propose several ideas and questions to be tested and solved in the future. TAKE AWAY.