The active transport of membrane vesicles containing capsule precursors, melanin
pigment, and proteinases is important in virulence of the pathogenic Cryptococcus species, but other components of the virulence cargo, as well as their functions or regulatory mechanisms, remain unclear. More...
The active transport of membrane vesicles containing capsule precursors, melanin
pigment, and proteinases is important in virulence of the pathogenic Cryptococcus species, but other components of the virulence cargo, as well as their functions or regulatory mechanisms, remain unclear. We have previously found that the cryptococcal endocytic protein Cin1 governs a unique Cin1-Wsp1-Cdc42 endocytic pathway required for intracellular transport and virulence. Using next generation sequencing, we compared the profiles of extracellular RNA (exRNA), including microRNAs (miRNAs), small interference RNAs (siRNAs), long noncoding RNA (lncRNA), and messenger RNA (mRNA) encapsulated in extracellular vesicles (EVs) between the C. deneoformans wild-type JEC21 and cin1 mutant strains. A total of 712 miRNAs and 88 siRNAs were identified from JEC21, and 799 miRNAs and 66 siRNAs from cin1. Differential expression screening revealed that the disruption of CIN1 results in many changes in exRNA expression. Gene Ontology (GO) and KEGG pathway enrichment analyses of differentially expressed miRNA target genes showed that endocytosis is one of the pathways most affected. Additionally, 690 extracellular lncRNAs and 8,994 mRNAs were identified from EVs of C. deneoformans. Of which, 572 lncRNAs and 7,721 mRNAs were from JEC21, and 584 lncRNAs and 7,703 mRNAs from cin1. Consistent with small exRNA annotation analysis, GO term and KEGG pathway enrichment analyses of differentially expressed mRNA genes indicated that endocytosis is the most affected pathway by CIN1 gene disruption. Taken together, we provided a comprehensive reference for that Cryptococcus species secrete abundant exRNA encapsulated in vesicles and that Cin1 plays a critical role in regulating secretion. In viewing of the growing significance of EVs and exRNAs in cell-cell communication, our study underscores the importance of exploring EV and exRNA technology in studies of Cryptococcus pathogenesis and discoveries of new treatment strategies. Less...