title: Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma.
abstract: 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 re-programming of transcript length between 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 of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed 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.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Gilmore
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Voorhies
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Dana
authors.initials: D
authors.lastname: Gebhart
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Anita
authors.initials: A
authors.lastname: Sil
mesh_terms: D005656:Fungal Proteins / Q000096:biosynthesis; D015966:Gene Expression Regulation, Fungal; D006658:Histoplasma / Q000235:genetics* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D012270:Ribosomes / Q000235:genetics; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D005656:Fungal Proteins; D012333:RNA, Messenger