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Cell. 2014 Sep 11;158(6):1281-1292. doi: 10.1016/j.cell.2014.08.011.

A dual program for translation regulation in cellular proliferation and differentiation.

Author information

1
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
2
Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
3
Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
4
Department of Hematology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
5
Department of Urology, Aarhus University Hospital, 8000 Aarhus, Denmark.
6
Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Surgery, Aarhus University Hospital, 8000 Aarhus, Denmark.
7
Department of Pediatric Oncology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.
8
Department of Neurosurgery, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, 1007 MB Amsterdam, the Netherlands; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
9
Department of Pathology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
10
Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark; Center for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark; The Danish Stem Cell Center (Danstem), University of Copenhagen, 2200 Copenhagen, Denmark.
11
Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
12
Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark; Bioinformatics Research Centre, Aarhus University Hospital, 8000 Aarhus, Denmark.
13
Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: anders.lund@bric.ku.dk.
14
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: pilpel@weizmann.ac.il.

Abstract

A dichotomous choice for metazoan cells is between proliferation and differentiation. Measuring tRNA pools in various cell types, we found two distinct subsets, one that is induced in proliferating cells, and repressed otherwise, and another with the opposite signature. Correspondingly, we found that genes serving cell-autonomous functions and genes involved in multicellularity obey distinct codon usage. Proliferation-induced and differentiation-induced tRNAs often carry anticodons that correspond to the codons enriched among the cell-autonomous and the multicellularity genes, respectively. Because mRNAs of cell-autonomous genes are induced in proliferation and cancer in particular, the concomitant induction of their codon-enriched tRNAs suggests coordination between transcription and translation. Histone modifications indeed change similarly in the vicinity of cell-autonomous genes and their corresponding tRNAs, and in multicellularity genes and their tRNAs, suggesting the existence of transcriptional programs coordinating tRNA supply and demand. Hence, we describe the existence of two distinct translation programs that operate during proliferation and differentiation.

PMID:
25215487
DOI:
10.1016/j.cell.2014.08.011
[Indexed for MEDLINE]
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