Altered nuclear tRNA metabolism in La-deleted S. pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.

Deletion of the sla1+ gene, which encodes a homolog of the human RNA binding protein, La, in S. 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 (EMM). A subset of these AAM genes is under control of the AP-1-like, stress responsive transcription factors, Atf1p and Pcr1p. While 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 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 over-expression of S. pombe los1+, (a.k.a., 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 S. cerevisiae.
Date: Dec. 07, 2011
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