title: Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex.
abstract: The current understanding of gene expression considers transcription and translation to be independent processes. Challenging this notion, we found that translation efficiency is determined during transcription elongation through the imprinting of mRNAs with Not1, the central scaffold of the Ccr4-Not complex. We determined that another subunit of the complex, Not5, defines Not1 binding to specific mRNAs, particularly those produced from ribosomal protein genes. This imprinting mechanism specifically regulates ribosomal protein gene expression, which in turn determines the translational capacity of cells. We validate our model by SILAC and polysome profiling experiments. As a proof of concept, we demonstrate that enhanced translation compensates for transcriptional elongation stress. Taken together, our data indicate that in addition to defining mRNA stability, components of the Ccr4-Not imprinting complex regulate RNA translatability, thus ensuring global gene expression homeostasis.
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
authors.forename: Ishaan
authors.initials: I
authors.lastname: Gupta
authors.affiliation: Department of Microbiology and Molecular Medicine, Faculty of Medicine, Institute of Genetics and Genomics, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Villanyi
authors.affiliation: Department of Microbiology and Molecular Medicine, Faculty of Medicine, Institute of Genetics and Genomics, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Sari
authors.initials: S
authors.lastname: Kassem
authors.affiliation: Genome Sciences Center, British Columbia Cancer Research Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Hughes
authors.affiliation: Department of Microbiology and Molecular Medicine, Faculty of Medicine, Institute of Genetics and Genomics, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Olesya O
authors.initials: OO
authors.lastname: Panasenko
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Stanford Genome Technology Center, Stanford University, Palo Alto, CA 94304, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
authors.affiliation: Department of Microbiology and Molecular Medicine, Faculty of Medicine, Institute of Genetics and Genomics, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: martine.collart@unige.ch.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Collart
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C079592:CDC39 protein, S cerevisiae; D018797:Cell Cycle Proteins; C111175:NOT5 protein, S cerevisiae; D012331:RNA, Fungal; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases