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Cell Rep. 2016 May 24;15(8):1782-94. doi: 10.1016/j.celrep.2016.04.055. Epub 2016 May 12.

Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex.

Author information

1
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany.
2
Department of Microbiology and Molecular Medicine, Faculty of Medicine, Institute of Genetics and Genomics, University of Geneva, 1211 Geneva 4, Switzerland.
3
Genome Sciences Center, British Columbia Cancer Research Agency, Vancouver, BC V5Z 1L3, Canada.
4
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.
5
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.

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.

PMID:
27184853
PMCID:
PMC4880543
DOI:
10.1016/j.celrep.2016.04.055
[Indexed for MEDLINE]
Free PMC Article

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