Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae

The ARGRIII gene of Saccharomyces cerevisiae encodes a transcriptional regu lator that also has inositol polyphosphate multikinase (ipmk) activity [Sai ardi et al, (1999) Curr, Biol, 9, 1323-1326]. To investigate how inositol p hosphates regulate gene expression, we disrupted the ARGRIII gene. This mut ation impaired nuclear mRNA export, slowed cell growth, increased cellular [InsP(3)] 170-fold and decreased [InsP(6)] 100-fold, indicating reduced pho sphorylation of InsP(3) to InsP(6). Levels of diphosphoinositol polyphospha tes were decreased much less dramatically than was InsP(6). Low levels of I nsP(6), and considerable quantities of Ins(1,3,4,5)P-4, were synthesized by an ipmk-independent route. Transcriptional control by ipmk reflects that i t is a pivotal regulator of nuclear mRNA export via inositol phosphate meta bolism. (C) 2000 Federation of European Biochemical Societies.