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The leucine-NH4.sup.+ uptake regulator Any1 limits growth as part of a general amino acid control response to loss of La protein by fission yeast

PloS one, 2021-06, Vol.16 (6), p.e0253494 [Peer Reviewed Journal]

COPYRIGHT 2021 Public Library of Science ;ISSN: 1932-6203 ;EISSN: 1932-6203 ;DOI: 10.1371/journal.pone.0253494

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  • Title:
    The leucine-NH4.sup.+ uptake regulator Any1 limits growth as part of a general amino acid control response to loss of La protein by fission yeast
  • Author: Cherkasova, Vera ; Iben, James R ; Pridham, Kevin J ; Kessler, Alan C ; Maraia, Richard J
  • Subjects: Amino acids ; Analysis ; Gene expression ; Transfer RNA
  • Is Part Of: PloS one, 2021-06, Vol.16 (6), p.e0253494
  • Description: The sla1.sup.+ gene of Schizosachharoymces pombe encodes La protein which promotes proper processing of precursor-tRNAs. Deletion of sla1 (sla1[DELTA]) leads to disrupted tRNA processing and sensitivity to target of rapamycin (TOR) inhibition. Consistent with this, media containing NH4.sup.+ inhibits leucine uptake and growth of sla1[DELTA] cells. Here, transcriptome analysis reveals that genes upregulated in sla1[DELTA] cells exhibit highly significant overalp with general amino acid control (GAAC) genes in relevant transcriptomes from other studies. Growth in NH4.sup.+ media leads to additional induced genes that are part of a core environmental stress response (CESR). The sla1[DELTA] GAAC response adds to evidence linking tRNA homeostasis and broad signaling in S. pombe. We provide evidence that deletion of the Rrp6 subunit of the nuclear exosome selectively dampens a subset of GAAC genes in sla1[DELTA] cells suggesting that nuclear surveillance-mediated signaling occurs in S. pombe. To study the NH4.sup.+ -effects, we isolated sla1[DELTA] spontaneous revertants (SSR) of the slow growth phenotype and found that GAAC gene expression and rapamycin hypersensitivity were also reversed. Genome sequencing identified a F32V substitution in Any1, a known negative regulator of NH4.sup.+ -sensitive leucine uptake linked to TOR. We show that .sup.3 H-leucine uptake by SSR-any1-F32V cells in NH4.sup.+ -media is more robust than by sla1[DELTA] cells. Moreover, F32V may alter any1.sup.+ function in sla1[DELTA] vs. sla1.sup.+ cells in a distinctive way. Thus deletion of La, a tRNA processing factor leads to a GAAC response involving reprogramming of amino acid metabolism, and isolation of the any1-F32V rescuing mutant provides an additional specific link.
  • Publisher: Public Library of Science
  • Language: English
  • Identifier: ISSN: 1932-6203
    EISSN: 1932-6203
    DOI: 10.1371/journal.pone.0253494
  • Source: PLoS OA刊
    Geneva Foundation Free Medical Journals at publisher websites
    PubMed Central
    ProQuest Central
    DOAJ Directory of Open Access Journals
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