<scp>RNA</scp> biology and the adaptation of <i>Cryptococcus neoformans</i> to host temperature and stress

Bloom, Amanda L. M.; Panepinto, John C.

doi:10.1002/wrna.1219

Cited by 9 publications

(8 citation statements)

References 78 publications

(150 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study identifies the cytoplasmic exonuclease Xrn1p as a regulator of multiple virulence factors in C. neoformans , extending previous studies that have found a central role for RNA metabolic processes in stress adaptation and virulence in this fungus (see (Bloom and Panepinto 2014) for a recent review).…”

Section: Discussionsupporting

confidence: 84%

Distinct and redundant roles of exonucleases in Cryptococcus neoformans: Implications for virulence and mating

Wollschlaeger

Trevijano-Contador

Wang

et al. 2014

Fungal Genetics and Biology

View full text Add to dashboard Cite

Opportunistic pathogens like Cryptococcus neoformans are constantly exposed to changing environments, in their natural habitat as well as when encountering a human host. This requires a coordinated program to regulate gene expression that can act at the levels of mRNA synthesis and also mRNA degradation. Here, we find that deletion of the gene encoding the major cytoplasmic 5’→3’ exonuclease Xrn1p in C. neoformans has important consequences for virulence associated phenotypes such as growth at 37°C, capsule and melanin. In an invertebrate model of cryptococcosis the alteration of these virulence properties corresponds to avirulence of the xrn1Δ mutant strains. Additionally, deletion of XRN1 impairs uni- and bisexual mating. On a molecular level, the absence of XRN1 is associated with the upregulation of other major exonuclease encoding genes (i.e. XRN2 and RRP44). Using inducible alleles of RRP44 and XRN2, we show that artificial overexpression of these genes alters LAC1 gene expression and mating. Our data thus suggest the existence of a complex interdependent regulation of exonuclease encoding genes that impact upon virulence and mating in C. neoformans.

show abstract

Section: Discussionsupporting

confidence: 84%

Distinct and redundant roles of exonucleases in Cryptococcus neoformans: Implications for virulence and mating

Wollschlaeger

Trevijano-Contador

Wang

et al. 2014

Fungal Genetics and Biology

View full text Add to dashboard Cite

show abstract

“…The previous work has characterized the family of chitin synthase genes and shown that chitin and chitosan levels accumulate along with population density in C. neoformans , unlike the budding yeasts S. cerevisiae and Candida albicans (Banks et al 2005 ). The CHS3 gene is highly expressed in proliferating C. neoformans cells, and single chs3 mutants are temperature sensitive at 37 °C, which is a highly relevant virulence factor for human infection (Bloom and Panepinto 2014 ). In addition to the previous work on steady-state expression levels of chitin synthase genes from asynchronous C. neoformans cells (Banks et al 2005 : Figure 3), the cell-cycle time series data set now provides much more dynamical detail.…”

Section: Chitin Synthesis In C Neoformans May Be mentioning

confidence: 99%

Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans

Kelliher

Haase

2017

Curr Genet

View full text Add to dashboard Cite

Proliferation and host evasion are critical processes to understand at a basic biological level for improving infectious disease treatment options. The human fungal pathogen Cryptococcus neoformans causes fungal meningitis in immunocompromised individuals by proliferating in cerebrospinal fluid. Current antifungal drugs target “virulence factors” for disease, such as components of the cell wall and polysaccharide capsule in C. neoformans. However, mechanistic links between virulence pathways and the cell cycle are not as well studied. Recently, cell-cycle synchronized C. neoformans cells were profiled over time to identify gene expression dynamics (Kelliher et al., PLoS Genet 12(12):e1006453, 2016). Almost 20% of all genes in the C. neoformans genome were periodically activated during the cell cycle in rich media, including 40 genes that have previously been implicated in virulence pathways. Here, we review important findings about cell-cycle-regulated genes in C. neoformans and provide two examples of virulence pathways—chitin synthesis and G-protein coupled receptor signaling—with their putative connections to cell division. We propose that a “comparative functional genomics” approach, leveraging gene expression timing during the cell cycle, orthology to genes in other fungal species, and previous experimental findings, can lead to mechanistic hypotheses connecting the cell cycle to fungal virulence.

show abstract

“…In response to host temperature, mRNAs encoding ribosomal proteins (RPs) are rapidly degraded in C. neoformans 15,16 . This enhanced mRNA decay lasts 1 h, contributing to a transient repression of RP transcripts.…”

Section: Introductionmentioning

confidence: 99%

Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming

et al. 2019

Self Cite

View full text Add to dashboard Cite

A common feature shared by systemic fungal pathogens of environmental origin, such as Cryptococcus neoformans, is their ability to adapt to mammalian core body temperature. In C. neoformans, this adaptation is accompanied by Ccr4-mediated decay of ribosomal protein mRNAs. Here we use the related, but thermo-intolerant species Cryptococcus amylolentus to demonstrate that this response contributes to host-temperature adaptation and pathogenicity of cryptococci. In a C. neoformans ccr4Δ mutant, stabilized ribosomal protein mRNAs are retained in the translating pool, and stress-induced transcriptomic changes are reduced in comparison with the wild type strain, likely due to ineffective translation of transcription factors. In addition, the mutant displays increased exposure of cell wall glucans, and recognition by Dectin-1 results in increased phagocytosis by lung macrophages, linking mRNA decay to adaptation and immune evasion.

show abstract

RNA biology and the adaptation of Cryptococcus neoformans to host temperature and stress

Cited by 9 publications

References 78 publications

Distinct and redundant roles of exonucleases in Cryptococcus neoformans: Implications for virulence and mating

Distinct and redundant roles of exonucleases in Cryptococcus neoformans: Implications for virulence and mating

Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans

Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming

Contact Info

Product

Resources

About