title: A dual program for translation regulation in cellular proliferation and differentiation.
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.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Gingold
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Disa
authors.initials: D
authors.lastname: Tehler
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Nanna R
authors.initials: NR
authors.lastname: Christoffersen
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Morten M
authors.initials: MM
authors.lastname: Nielsen
authors.affiliation: Department of Hematology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Fazila
authors.initials: F
authors.lastname: Asmar
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Kooistra
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Nicolaj S
authors.initials: NS
authors.lastname: Christophersen
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Christensen
authors.affiliation: Department of Urology, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Borre
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Karina D
authors.initials: KD
authors.lastname: Sørensen
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Lars D
authors.initials: LD
authors.lastname: Andersen
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Surgery, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Claus L
authors.initials: CL
authors.lastname: Andersen
authors.affiliation: Department of Pediatric Oncology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center, 1007 MB Amsterdam, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Hulleman
authors.affiliation: 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.
authors.forename: Tom
authors.initials: T
authors.lastname: Wurdinger
authors.affiliation: Department of Pathology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiær
authors.affiliation: 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.
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
authors.affiliation: Department of Hematology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Ørntoft
authors.affiliation: Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Waszak
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Orna
authors.initials: O
authors.lastname: Dahan
authors.affiliation: Department for Molecular Medicine, Aarhus University Hospital, 8000 Aarhus, Denmark; Bioinformatics Research Centre, Aarhus University Hospital, 8000 Aarhus, Denmark.
authors.forename: Jakob Skou
authors.initials: JS
authors.lastname: Pedersen
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: anders.lund@bric.ku.dk.
authors.forename: Anders H
authors.initials: AH
authors.lastname: Lund
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: pilpel@weizmann.ac.il.
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Pilpel
mesh_terms: D000926:Anticodon; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003062:Codon; D006657:Histones / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000926:Anticodon; D003062:Codon; D006657:Histones; D012333:RNA, Messenger; D012343:RNA, Transfer