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Uncoupling of mRNA synthesis and degradation impairs adaptation to host temperature in C ryptococcus neoformans
Author(s) -
Bloom Amanda L. M.,
Solomons J. T. Graham,
Havel Virginia E.,
Panepinto John C.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12258
Subject(s) - biology , transcription (linguistics) , messenger rna , cryptococcus neoformans , virulence , mutant , rna polymerase ii , psychological repression , ribosomal protein , microbiology and biotechnology , rna , gene expression , genetics , promoter , gene , ribosome , philosophy , linguistics
Summary The pathogenic fungus C ryptococcus neoformans must overcome multiple stressors to cause disease in its human host. In this study, we report that C . neoformans rapidly and transiently repressed ribosomal protein ( RP ) transcripts during a transition from 30° C to host temperature. This repression was accompanied by accelerated mRNA degradation mediated by the major deadenylase, Ccr 4, and influenced by the dissociable RNA polymerase II subunit, Rpb 4. Destabilization and deadenylation of RP transcripts were impaired in an rpb4 Δ mutant, suggesting that Rpb 4 may be involved in host temperature‐induced Ccr 4‐mediated decay. Accelerated decay of ER stress transcripts 1 h following a shift to host temperature was also impaired in the rpb4 Δ mutant. In response to host temperature, Rpb 4 moved from the nucleus to the cytoplasm, supporting a role for Rpb 4 in coupling transcription and degradation. The PKH signalling pathway was implicated as a regulator of accelerated degradation of the RP transcripts, but not of the ER stress transcripts, revealing a further level of specificity. When transcription and degradation were uncoupled by deletion of Rpb 4, growth at host temperature was impaired and virulence was attenuated. These data suggest that mRNA synthesis and decay are coupled in C . neoformans via Rpb 4, and this tight coordination promotes host‐temperature adaptation and pathogenicity.