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A dual program for translation regulation in cellular proliferation and differentiation

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  • Hila Gingold, Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel., Unknown
  • Disa Tehler, University of Copenhagen, Unknown
  • Nanna R Christoffersen, University of Copenhagen, Unknown
  • Morten M Nielsen
  • Fazila Asmar, University of Copenhagen, Unknown
  • Susanne M Kooistra, University of Copenhagen, Unknown
  • Nicolaj S Christophersen, University of Copenhagen, Unknown
  • Lise Lotte Christensen
  • ,
  • Michael Borre
  • Karina D Sørensen
  • Lars D Andersen
  • Claus L Andersen
  • Esther Hulleman, Department of Pediatric Oncology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, 1007 MB Amsterdam, the Netherlands., Unknown
  • Tom Wurdinger, 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., Unknown
  • Elisabeth Ralfkiær, Department of Pathology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
  • ,
  • Kristian Helin, University of Copenhagen, Denmark
  • Kirsten Grønbæk, University of Copenhagen, Unknown
  • Torben Orntoft
  • Sebastian M Waszak, École Polytechnique Fédérale de Lausanne, Unknown
  • Orna Dahan, Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel., Unknown
  • Jakob Skou Pedersen
  • Anders H Lund, University of Copenhagen, Denmark
  • Yitzhak Pilpel, Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: pilpel@weizmann.ac.il., Unknown

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.

Original languageEnglish
JournalCell
Volume158
Issue6
Pages (from-to)1281-92
Number of pages12
ISSN0092-8674
DOIs
Publication statusPublished - 11 Sep 2014

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