title: The cellular growth rate controls overall mRNA turnover, and modulates either transcription or degradation rates of particular gene regulons.
abstract: We analyzed 80 different genomic experiments, and found a positive correlation between both RNA polymerase II transcription and mRNA degradation with growth rates in yeast. Thus, in spite of the marked variation in mRNA turnover, the total mRNA concentration remained approximately constant. Some genes, however, regulated their mRNA concentration by uncoupling mRNA stability from the transcription rate. Ribosome-related genes modulated their transcription rates to increase mRNA levels under fast growth. In contrast, mitochondria-related and stress-induced genes lowered mRNA levels by reducing mRNA stability or the transcription rate, respectively. We also detected these regulations within the heterogeneity of a wild-type cell population growing in optimal conditions. The transcriptomic analysis of sorted microcolonies confirmed that the growth rate dictates alternative expression programs by modulating transcription and mRNA decay.The regulation of overall mRNA turnover keeps a constant ratio between mRNA decay and the dilution of [mRNA] caused by cellular growth. This regulation minimizes the indiscriminate transmission of mRNAs from mother to daughter cells, and favors the response capacity of the latter to physiological signals and environmental changes. We also conclude that, by uncoupling mRNA synthesis from decay, cells control the mRNA abundance of those gene regulons that characterize fast and slow growth.
authors.affiliation: Departamento de Genética, Facultad de Ciencias Biológicas, Universitat de València. C/ Dr. Moliner 50. E46100, Burjassot, Spain ERI Biotecmed, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain.
authors.forename: José
authors.initials: J
authors.lastname: García-Martínez
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, C/ Antonio Maura Montaner, E41013 Sevilla Departamento de Genética, Universidad de Sevilla, Avenida de la Reina Mercedes s/n, E41012, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Delgado-Ramos
authors.affiliation: Departamento de Estadística e Investigación Operativa, Facultad de Matemáticas, Universitat de València. C/ Dr. Moliner 50. E46100, Burjassot, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ayala
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Vicent
authors.initials: V
authors.lastname: Pelechano
authors.affiliation: ERI Biotecmed, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Medina
authors.affiliation: ERI Biotecmed, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain.
authors.forename: Fany
authors.initials: F
authors.lastname: Carrasco
authors.affiliation: Instituto de Ciencias de la Vid y del Vino (CSIC, Universidad de La Rioja, Gobierno de La Rioja), Finca La Grajera LO-20 Salida 13, Autovía del Camino de Santiago, E26007 Logroño, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: González
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, C/ Antonio Maura Montaner, E41013 Sevilla.
authors.forename: Eduardo
authors.identifier: http://orcid.org/0000-0002-0621-9914
authors.initials: E
authors.lastname: Andrés-León
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany Stanford University School of Medicine, Department of Genetics, Stanford, CA 94305, USA Stanford Genome Technology Center, 3165 Porter Dr. Palo Alto, CA 94305, USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Steinmetz
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Medicinaregatan 9 c, 40530 Göteborg, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Warringer
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, C/ Antonio Maura Montaner, E41013 Sevilla Departamento de Genética, Universidad de Sevilla, Avenida de la Reina Mercedes s/n, E41012, Spain jose.e.perez@uv.es.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
authors.affiliation: ERI Biotecmed, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universitat de Valencia. C/ Dr. Moliner 50. E46100, Burjassot, Spain jose.e.perez@uv.es.
authors.forename: José E
authors.identifier: http://orcid.org/0000-0002-1992-513X
authors.initials: JE
authors.lastname: Pérez-Ortín
mesh_terms: D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D020459:Genes, rRNA; D001678:Organelle Biogenesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018085:Regulon; D012270:Ribosomes / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C510155:PUF3 protein, S cerevisiae; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins