Dataset Information

Long Non-Coding RNAs in Cryptococcus neoformans: Insights Into Fungal Pathogenesis.

ABSTRACT: Long non-coding RNAs (lncRNAs) are highly expressed and can modulate multiple cellular processes including transcription, splicing, translation, and many diverse signaling events. LncRNAs can act as sponges for miRNAs, RNA and DNA binding proteins, functioning as competitive endogenous RNAs. The contribution of lncRNAs to microbial pathogenesis is largely neglected in eukaryotic pathogens despite the abundance of RNA sequencing datasets encompassing conditions of stress, gene deletions and conditions that mimic the host environment. The human fungal pathogen Cryptococcus neoformans encodes 6975 (84%) protein-coding and 1359 (16%) non-protein-coding RNAs, of which 1182 (14.2%) are lncRNAs defined by a threshold of greater than 200 nucleotides in length. Here, we discuss the current state of knowledge in C. neoformans lncRNA biology. Utilizing existing RNA seq datasets, we examine trends in lncRNA expression and discuss potential implications for pathogenesis.

SUBMITTER: Kalem MC

PROVIDER: S-EPMC8968117 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Long Non-Coding RNAs in <i>Cryptococcus neoformans</i>: Insights Into Fungal Pathogenesis.

Kalem Murat C MC Panepinto John C JC

Frontiers in cellular and infection microbiology 20220317

Long non-coding RNAs (lncRNAs) are highly expressed and can modulate multiple cellular processes including transcription, splicing, translation, and many diverse signaling events. LncRNAs can act as sponges for miRNAs, RNA and DNA binding proteins, functioning as competitive endogenous RNAs. The contribution of lncRNAs to microbial pathogenesis is largely neglected in eukaryotic pathogens despite the abundance of RNA sequencing datasets encompassing conditions of stress, gene deletions and condi ...[more]

PMID: 35372111

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Project description:Chitin is an essential component of the cell wall of Cryptococcus neoformans conferring structural rigidity and integrity under diverse environmental conditions. Chitin deacetylase genes encode the enyzmes (chitin deacetylases [Cdas]) that deacetylate chitin, converting it to chitosan. The functional role of chitosan in the fungal cell wall is not well defined, but it is an important virulence determinant of C. neoformans Mutant strains deficient in chitosan are completely avirulent in a mouse pulmonary infection model. C. neoformans carries genes that encode three Cdas (Cda1, Cda2, and Cda3) that appear to be functionally redundant in cells grown under vegetative conditions. Here we report that C. neoformans Cda1 is the principal Cda responsible for fungal pathogenesis. Point mutations were introduced in the active site of Cda1 to generate strains in which the enzyme activity of Cda1 was abolished without perturbing either its stability or localization. When used to infect CBA/J mice, Cda1 mutant strains produced less chitosan and were attenuated for virulence. We further demonstrate that C. neoformans Cda genes are transcribed differently during a murine infection from what has been measured in vitroIMPORTANCECryptococcus neoformans is unique among fungal pathogens that cause disease in a mammalian host, as it secretes a polysaccharide capsule that hinders recognition by the host to facilitate its survival and proliferation. Even though it causes serious infections in immunocompromised hosts, reports of infection in hosts that are immunocompetent are on the rise. The cell wall of a fungal pathogen, its synthesis, composition, and pathways of remodelling are attractive therapeutic targets for the development of fungicides. Chitosan, a polysaccharide in the cell wall of C. neoformans is one such target, as it is critical for pathogenesis and absent in the host. The results we present shed light on the importance of one of the chitin deacetylases that synthesize chitosan during infection and further implicates chitosan as being a critical factor for the pathogenesis of C. neoformans.

Dataset Information

Long Non-Coding RNAs in Cryptococcus neoformans: Insights Into Fungal Pathogenesis.

Publications

Long Non-Coding RNAs in <i>Cryptococcus neoformans</i>: Insights Into Fungal Pathogenesis.

Similar Datasets

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