在人体温度下,真菌病原体白色念珠菌可以响应宿主相关的线索从酵母转变为丝状形态。此外,在高热发作期间遇到的升高的温度可以独立地诱导白色念珠菌成丝。然而,控制这种响应温度升高的发育转变的潜在遗传途径仍未被探索。这里,我们进行了功能性基因组筛选,以解开基因机制协调白色念珠菌成丝,特别是响应升高的温度,在此过程中涉及与剪接体或前mRNA剪接相关的45%的基因。使用RNA-Seq阐明mRNA剪接和成丝之间的关系,我们发现,与酵母相比,细丝中内含子的保留水平更高,这与受影响基因的表达降低有关。有趣的是,与野生型相比,编码对成丝重要的剪接体成分(PRP19)的基因的纯合缺失导致甚至更高水平的内含子保留,并显示出全局失调的基因表达。这表明内含子保留是在成丝过程中微调基因表达的机制,剪接体的扰动加剧了这一过程并阻止了成丝。总的来说,这项研究揭示了一种新的控制白色念珠菌成丝的生物过程,为这一关键毒力性状的复杂调控提供了新的见解。重要真菌病原体如白念珠菌可引起严重感染,在免疫功能低下的个体中具有高死亡率。当白色念珠菌在人类发热发作期间遇到的温度下生长时,酵母细胞经历了向丝状细胞的转变,这个过程是其毒力的关键。这里,我们扩展了我们对白色念珠菌如何响应升高的温度而经历成丝的理解,并鉴定了许多参与mRNA剪接的基因,这些基因正调节成丝。通过转录组分析,我们发现内含子保留是一种微调细丝中基因表达的机制,剪接体的扰动会加剧内含子的保留并大幅改变基因表达,导致丝状阻塞。这项工作增加了关于内含子在真菌中的作用的不断增长的知识,并为调节白色念珠菌关键毒力性状的细胞过程提供了新的见解。
At human body temperature, the fungal pathogen Candida albicans can transition from yeast to filamentous morphologies in response to host-relevant cues. Additionally, elevated temperatures encountered during febrile episodes can independently induce C. albicans filamentation. However, the underlying genetic pathways governing this developmental transition in response to elevated temperatures remain largely unexplored. Here, we conducted a functional genomic screen to unravel the genetic mechanisms orchestrating C. albicans filamentation specifically in response to elevated temperature, implicating 45% of genes associated with the
spliceosome or pre-mRNA splicing in this process. Employing RNA-Seq to elucidate the relationship between mRNA splicing and filamentation, we identified greater levels of intron retention in filaments compared to yeast, which correlated with reduced expression of the affected genes. Intriguingly, homozygous deletion of a gene encoding a
spliceosome component important for filamentation (PRP19) caused even greater levels of intron retention compared with wild type and displayed globally dysregulated gene expression. This suggests that intron retention is a mechanism for fine-tuning gene expression during filamentation, with perturbations of the
spliceosome exacerbating this process and blocking filamentation. Overall, this study unveils a novel biological process governing C. albicans filamentation, providing new insights into the complex regulation of this key virulence trait.IMPORTANCEFungal pathogens such as Candida albicans can cause serious infections with high mortality rates in immunocompromised individuals. When C. albicans is grown at temperatures encountered during human febrile episodes, yeast cells undergo a transition to filamentous cells, and this process is key to its virulence. Here, we expanded our understanding of how C. albicans undergoes filamentation in response to elevated temperature and identified many genes involved in mRNA splicing that positively regulate filamentation. Through transcriptome analyses, we found that intron retention is a mechanism for fine-tuning gene expression in filaments, and perturbation of the
spliceosome exacerbates intron retention and alters gene expression substantially, causing a block in filamentation. This work adds to the growing body of knowledge on the role of introns in fungi and provides new insights into the cellular processes that regulate a key virulence trait in C. albicans.