GTPase Npa3‐ TORC1 crosstalk suggests genetic coordination of nutrient sensing and translational control

The GPN-loop GTPase Npa3 plays a critical role in RNA polymerase II (RNAPII) assembly and nuclear import. We employed here the npa3ΔC mutant, which supports normal RNAPII localization and function, to investigate potential links between Npa3 and target of rapamycin complex I (TORC1) signaling. The npa3ΔC cells exhibited increased sensitivity to rapamycin, a synthetic sickness interaction with tor1Δ, and a delayed growth recovery rate from rapamycin-induced G1 arrest. Co-expression analysis identified LTV1, a gene involved in TORC1 signaling and ribosome nuclear export, as one of the top genes co-expressed with NPA3. Furthermore, overexpression of eukaryotic translation initiation factor 1A (eIF1A, TIF11) or regulator of heterotrimeric G-protein signaling (RGS2) restored growth in npa3ΔC cells under rapamycin treatment. Interestingly, RGS2 also rescued growth under hygromycin B stress. Our findings suggest a genetic interplay between Npa3 and TORC1.