Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes

Dichtl, Bernhard, Stevens, Audrey and Tollervey, David 1997, Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes, EMBO journal, vol. 16, no. 23, pp. 7184-7195, doi: 10.1093/emboj/16.23.7184.

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Title Lithium toxicity in yeast is due to the inhibition of RNA processing enzymes
Author(s) Dichtl, BernhardORCID iD for Dichtl, Bernhard
Stevens, Audrey
Tollervey, David
Journal name EMBO journal
Volume number 16
Issue number 23
Start page 7184
End page 7195
Total pages 12
Publisher Nature Publishing Group
Place of publication London, England
Publication date 1997-12-01
ISSN 0261-4189
Keyword(s) exonucleases
RNA processing
sulfate assimilation
Summary Hal2p is an enzyme that converts pAp (adenosine 3',5' bisphosphate), a product of sulfate assimilation, into 5' AMP and Pi. Overexpression of Hal2p confers lithium resistance in yeast, and its activity is inhibited by submillimolar amounts of Li+in vitro. Here we report that pAp accumulation in HAL2 mutants inhibits the 5'3' exoribonucleases Xrn1p and Rat1p. Li+ treatment of a wild-type yeast strain also inhibits the exonucleases, as a result of pAp accumulation due to inhibition of Hal2p; 5' processing of the 5.8S rRNA and snoRNAs, degradation of pre-rRNA spacer fragments and mRNA turnover are inhibited. Lithium also inhibits the activity of RNase MRP by a mechanism which is not mediated by pAp. A mutation in the RNase MRP RNA confers Li+ hypersensitivity and is synthetically lethal with mutations in either HAL2 or XRN1. We propose that Li+ toxicity in yeast is due to synthetic lethality evoked between Xrn1p and RNase MRP. Similar mechanisms may contribute to the effects of Li+ on development and in human neurobiology.
Language eng
DOI 10.1093/emboj/16.23.7184
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©1997, Nature Publishing Group
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