Opposing PKA and Hog1 signals control the post-transcriptional response to glucose availability in Cryptococcus neoformans

Mol Microbiol. 2016 Oct;102(2):306-320. doi: 10.1111/mmi.13461. Epub 2016 Aug 11.

Abstract

The pathogenic fungus Cryptococcus neoformans must adapt to glucose-limited conditions in the lung and glucose replete conditions upon dissemination to the brain. We report that glucose controls ribosome biogenesis and translation by modulating mRNA decay through a balance of PKA and Hog1 signalling. Glucose signalling through PKA stabilized ribosomal protein (RP) mRNAs whereas glucose starvation destabilized RP transcripts through Hog1. Glucose starvation-induced oxidative stress response genes, and treatment of glucose-fed cells with reactive oxygen species (ROS) generating compounds repressed RP transcripts, both of which were dependent on Hog1. Stabilization of RP transcripts led to retention of polysomes in a hog1Δ mutant, whereas stabilization of RP transcripts by cyclic AMP did not affect translation repression, suggesting that Hog1 alone signals translation repression. In sum, this work describes a novel antagonism between PKA and Hog1 controlling ribosome biogenesis via mRNA stability in response to glucose availability in this important human pathogen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cryptococcosis / metabolism
  • Cryptococcus neoformans / enzymology
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Fungal Proteins / metabolism
  • Glucose / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • RNA Stability
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Fungal Proteins
  • RNA, Messenger
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Glucose