{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kti12 is an evolutionarily conserved protein that functions as an accessory factor for the Elongator complex, playing a critical role in tRNA wobble uridine modification and thereby influencing protein synthesis and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Structural and biochemical studies have revealed that Kti12 contains an N‐terminal ATPase domain and a C‐terminal tRNA‐binding domain connected by a flexible linker; in some species, an atypical Walker A motif modulates its ATP affinity without abolishing catalytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Such domain organization is essential for maintaining Elongator integrity, as Kti12 is required for the association of accessory factors with the complex and for proper regulation of its phosphorylation state—a process linked to toxin sensitivity (e.g., zymocin) in yeast."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical function in tRNA modification, altered expression of Kti12 (also known as TOT4 in yeast) has been shown to either confer resistance or hypersensitivity to such toxins by modulating the phosphorylation status of Elongator subunits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, homologues in plants—such as the Arabidopsis DRL1 and poplar PtKTI12A/B—are induced under stress conditions (e.g., heat, drought) and affect levels of modified tRNA nucleosides, suggesting that Kti12 also contributes to stress responses and developmental regulation across eukaryotes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, genetic evidence implies that Kti12 may intersect with other cellular pathways including those involved in ceramide responses, reinforcing its multifaceted regulatory role beyond tRNA modification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies highlight Kti12 as a pivotal regulator that ensures proper Elongator complex function, influences tRNA modification dynamics, and integrates diverse cellular signals to maintain translational fidelity and stress adaptation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Marta Smejda, Dominika Kądziołka, Natalia Radczuk, et al. 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