Translational Control of Cell Division by Elongator

• Published in: Cell reports (Cambridge) Vol. 1; no. 5; pp. 424 - 433
• Main Authors: Bauer, Fanelie, Matsuyama, Akihisa, Candiracci, Julie, Dieu, Marc, Scheliga, Judith, Wolf, Dieter A., Yoshida, Minoru, Hermand, Damien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.2012; Elsevier
• Subjects: Cell Cycle Proteins - physiology; Cell Division - genetics; Cell Division - physiology; Codon - genetics; Codon - physiology; Cytokinesis - genetics; Cytokinesis - physiology; DNA-Binding Proteins - physiology; Histone Acetyltransferases - genetics; Histone Acetyltransferases - physiology; Lysine - genetics; Lysine - physiology; Mitosis - genetics; Mitosis - physiology; Protein Biosynthesis - genetics; Protein Biosynthesis - physiology; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - physiology; RNA, Transfer - genetics; RNA, Transfer - physiology; Schizosaccharomyces - cytology; Schizosaccharomyces - genetics; Schizosaccharomyces - physiology; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - physiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2012.04.001

Elongator is required for the synthesis of the mcm5s2 modification found on tRNAs recognizing AA-ending codons. In order to obtain a global picture of the role of Elongator in translation, we used reverse protein arrays to screen the fission yeast proteome for translation defects. Unexpectedly, this revealed that Elongator inactivation mainly affected three specific functional groups including proteins implicated in cell division. The absence of Elongator results in a delay in mitosis onset and cytokinesis defects. We demonstrate that the kinase Cdr2, which is a central regulator of mitosis and cytokinesis, is under translational control by Elongator due to the Lysine codon usage bias of the cdr2 coding sequence. These findings uncover a mechanism by which the codon usage, coupled to tRNA modifications, fundamentally contributes to gene expression and cellular functions. [Display omitted] ► A proteome-wide screen identified targets of Elongator, required for tRNA modification ► Absence of Elongator affects translation of specific functionally related mRNAs ► Translation of Cdr2, a central regulator of mitosis, is directly regulated by Elongator The inherent redundancy of the genetic code imposes the existence of synonymous codons, and a universal feature of gene expression is that synonymous codons are not used at the same frequency, a phenomenon referred to as the codon usage bias. Hermand and colleagues now find that codon usage bias, coupled to tRNA modification by Elongator, is used as a mechanism to coordinate the expression of groups of genes involved in specific pathways, including cell-cycle progression.