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General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4

Duncan, CDS; Rodriguez-Lopez, M; Ruis, P; Bahler, J; Mata, J; (2018) General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4. Proceedings of the National Academy of Sciences of the United States of America (PNAS) , 115 (8) E1829-E1838. 10.1073/pnas.1713991115. Green open access

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Abstract

Eukaryotes respond to amino acid starvation by enhancing the translation of mRNAs encoding b-ZIP family transcription factors (GCN4 in Saccharomyces cerevisiae and ATF4 in mammals), which launch transcriptional programs to counter this stress. This pathway involves phosphorylation of the eIF2 translation factor by Gcn2-protein kinases and is regulated by upstream ORFs (uORFs) in the GCN4/ATF4 5′ leaders. Here, we present evidence that the transcription factors that mediate this response are not evolutionarily conserved. Although cells of the fission yeast Schizosaccharomyces pombe respond transcriptionally to amino acid starvation, they lack clear Gcn4 and Atf4 orthologs. We used ribosome profiling to identify mediators of this response in S. pombe, looking for transcription factors that behave like GCN4. We discovered a transcription factor (Fil1) translationally induced by amino acid starvation in a 5′ leader and Gcn2-dependent manner. Like Gcn4, Fil1 is required for the transcriptional response to amino acid starvation, and Gcn4 and Fil1 regulate similar genes. Despite their similarities in regulation, function, and targets, Fil1 and Gcn4 belong to different transcription factor families (GATA and b-ZIP, respectively). Thus, the same functions are performed by nonorthologous proteins under similar regulation. These results highlight the plasticity of transcriptional networks, which maintain conserved principles with nonconserved regulators.

Type: Article
Title: General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.1713991115
Publisher version: https://doi.org/10.1073/pnas.1713991115
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, fission yeast, translational control, GCN4, ATF4, ribosome profiling, MESSENGER-RNA TRANSLATION, GENOME-WIDE ANALYSIS, SCHIZOSACCHAROMYCES-POMBE, MAMMALIAN-CELLS, ENVIRONMENTAL-STRESS, KINASE GCN2, EXPRESSION, PROTEIN, STARVATION, INITIATION
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10047829
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