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

The sla1 + gene of Schizosachharoymces pombe encodes La protein which promotes proper processing of precursor-tRNAs. Deletion of sla1 ( sla1 Δ) leads to disrupted tRNA processing and sensitivity to target of rapamycin (TOR) inhibition. Consistent with this, media containing NH4 + inhibits leucine uptake and growth of sla1 Δ cells. Here, transcriptome analysis reveals that genes upregulated in sla1 Δ cells exhibit highly significant overalp with general amino acid control (GAAC) genes in relevant transcriptomes from other studies. Growth in NH4 + media leads to additional induced genes that are part of a core environmental stress response (CESR). The sla1 Δ 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 Δ cells suggesting that nuclear surveillance-mediated signaling occurs in S . pombe . To study the NH4 + -effects, we isolated sla1 Δ 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 + -sensitive leucine uptake linked to TOR. We show that 3 H-leucine uptake by SSR- any1-F32V cells in NH4 + -media is more robust than by sla1 Δ cells. Moreover, F32V may alter any1 + function in sla1 Δ vs. sla1 + 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.