A dual program for translation regulation in cellular proliferation and differentiation

Hila Gingold, Disa Tehler, Nanna R. Christoffersen, Morten M. Nielsen, Fazila Asmar, Susanne M. Kooistra, Nicolaj S. Christophersen, Lise Lotte Christensen, Michael Borre, Karina D. Sørensen , Lars D. Andersen, Claus L. Andersen, Esther Hulleman, Thomas Wurdinger, Elisabeth Ralfkiær, Kirsten Grønbæk, Kristian Helin, Torben Ørntoft , Sebastian M. Waszak, Orna DahanJakob Skou Pedersen, Anders H. Lund, Yitzhak Pilpel

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)1281-1292
JournalCell
Volume158
Issue number6
DOIs
Publication statusPublished - 11 Sep 2014
Externally publishedYes

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