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Origin of translational control by eIF2α phosphorylation: insights from genome-wide translational profiling studies in fission yeast

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Abstract

During amino acid limitation, the protein kinase Gcn2 phosphorylates the α subunit of eIF2, thereby regulating mRNA translation. In yeast Saccharomyces cerevisiae and mammals, eIF2α phosphorylation regulates translation of related transcription factors Gcn4 and Atf4 through upstream open reading frames (uORFs) to activate transcription genome wide. However, mammals encode three more eIF2α kinases activated by distinct stimuli. Did the translational control system involving eIF2α phosphorylation evolve from so simple (as found in yeast S. cerevisiae) to complex (as found in humans)? Recent genome-wide translational profiling studies of amino acid starvation response in the fission yeast Schizosaccharomyces pombe provide an unexpected answer to this question.

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Fig. 1
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Adapted from Fig. S10B of Chikashige et al. (2020)

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adapted from Molecular Biology of the Gene, 7th edition. Right, translational regulatory motifs mediated by uORF-dependent control. In (B), Coherent FFL with AND node makes a persistent detector that only responds to a long-lived signal (Alon, 2007). However, Coherent FFL with OR node works differently, as described in the text

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Acknowledgements

I thank Hiroaki Kato (School of Medicine, Shimane University), Yuji Chikashige (National Institute of Information and Communications Technology, Kobe), Shintaro Iwasaki (RIKEN, Wako), and Richard Todd (Department of Plant Pathology, Kansas State University) for helpful discussion.

Funding

K-INBRE program Pilot Grant, National Institutes of Health [P20 GM103418]; National Institutes of Health R15 grant [GM125671]; National Science Foundation Research Grant [1412250]; JSPS KAKENHI [18K19963]; Kansas State University (KSU) Terry Johnson Cancer Center.

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  1. Molecular Cellular and Developmental Biology Program, Division of Biology, Kansas State University, Manhattan, KS, 66506, USA

    Katsura Asano

  2. Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8530, Japan

    Katsura Asano

  3. Hiroshima Research Center for Healthy Aging, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8530, Japan

    Katsura Asano

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Correspondence to Katsura Asano.

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Asano, K. Origin of translational control by eIF2α phosphorylation: insights from genome-wide translational profiling studies in fission yeast. Curr Genet 67, 359–368 (2021). https://doi.org/10.1007/s00294-020-01149-w

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