GSE68705
Genome-wide reprogramming of transcript architecture by temperature specifies the developmental states of the human pathogen Histoplasma [ribosome profiling]
Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel post-transcriptional mechanism of gene regulation in Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5’ leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements uncovered a class of differential leader transcripts that exhibit tight transcriptional and translational regulation. Further examination of these dually regulated genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature.  This series contains ribosomal footprinting data for Hc G217B. Overall design: mRNA libraries were prepared with or without ribosome footprinting for two biological replicates each from cells grown in the yeast or hyphal phase (8 samples total).