title: Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.
abstract: Deletion of the sla1(+) gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1(+) have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1-like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1(+) (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1(+) regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae.
authors.affiliation: Intramural Research Program on Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Cherkasova
authors.forename: Luis Lopez
authors.initials: LL
authors.lastname: Maury
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bacikova
authors.forename: Kevin
authors.initials: K
authors.lastname: Pridham
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Maraia
mesh_terms: D051697:Activating Transcription Factor 1 / Q000235:genetics / Q000378:metabolism*; D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D012331:RNA, Fungal / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012343:RNA, Transfer / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D051697:Activating Transcription Factor 1; D051696:Activating Transcription Factors; D028861:Nuclear Pore Complex Proteins; C097701:Pcr1 protein, S pombe; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C543934:Xpot protein, S pombe; C513614:sla1 protein, S pombe; D012343:RNA, Transfer