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 Delta) 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 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(+) 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(+)-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(+)-sensitive leucine uptake linked to TOR. We show that H-3-leucine uptake by SSR-any1-F32V cells in NH4(+)-media is more robust than by sla1 Delta cells. Moreover, F32V may alter any1(+) function in sla1 Delta 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.