KTI12 encodes a protein that associates with Elongator complex, a six-subunit histone acetytransferase complex that functions with the elongating form of RNA polymerase II during transcription (5, 7, 3). KTI12 was first identified in a screen for mutants insensitive to the Kluyveromyces lactis toxin zymocin, which causes cell cycle arrest in G1 phase (1, 2). Both mutation and overexpression of KTI12 were found to confer toxin resistance, in contrast to the other genes identified in the screen, whose overexpression did not confer resistance (1, 8). Loss of Kti12p function also results in slow growth at 30 degrees and temperature sensitivity above 38 degrees, and sensitivity to the cell wall poison Calcofluor White, the purine analog caffeine, and the nucleotide biosynthesis inhibitor 6-azauracil (6-AU; 2).

The pleiotropic phenotypes exhibited by kti12 mutants may be due in part to a requirement for Elongator complex, Kti11p, Kti12p, and Ats1p in synthesis of the 5-methoxycarbonylmethyl (mcm5) and 5-carbamoylmethyl (ncm5) groups that are added to uridine nucleosides located at the wobble position of tRNA during tRNA maturation (4). Absence of these modifications on tRNA affects decoding of mRNA. Kti12p has also been shown to interact with pyruvate kinase, Cdc19p, suggesting an involvement in regulating or coordinating carbon source metabolism and growth (3).

Biochemical and genetic data point to an important functional interaction between Kti12p and Elongator complex. A salt-labile physical interaction has been demonstrated (5). In addition, Kti12p interacts with the form of RNA polymerase II that is hyperphosphorylated on serine 5 of the C-terminal domain (CTD) repeats (3, 7). However, as deletion of Kti12p does not affect the structural integrity of the Elongator complex, and Kti12p does not copurify with Elongator, it is unlikely that Kti12p is a structural component of the complex (8, 5). Genetic experiments indicate that Kti12p is required for normal histone acetyltransferase activity of Elongator in vivo (5). Interactions between Kti12p and DNA have been reported to occur primarily in the promoter region rather than in coding sequences (3), while other work indicates that Kti12p is associated with chromatin throughout the genome (5). Kti12p has been proposed to play a regulatory role in Elongator function (8), an hypothesis supported by the finding that Kti12p antagonizes the action of the Sit4p phosphatase in dephosphorylation of the Iki3p subunit of Elongator (9).

Last updated: 2006-10-10