Department of Biology, Ball State University, Muncie, IN, 47306, USA.
Department of Mathematics, Ball State University, Muncie, IN, 47306, USA.
Yeast. 2019 Nov;36(11):669-677. doi: 10.1002/yea.3436. Epub 2019 Aug 16.
RNA can be modified in over 100 distinct ways, and these modifications are critical for function. Pseudouridine synthases catalyse pseudouridylation, one of the most prevalent RNA modifications. Pseudouridine synthase 7 modifies a variety of substrates in Saccharomyces cerevisiae including tRNA, rRNA, snRNA, and mRNA, but the substrates for other budding yeast Pus7 homologues are not known. We used CRISPR-mediated genome editing to disrupt Candida albicans PUS7 and find absence leads to defects in rRNA processing and a decrease in cell surface hydrophobicity. Furthermore, C. albicans Pus7 absence causes temperature sensitivity, defects in filamentation, altered sensitivity to antifungal drugs, and decreased virulence in a wax moth model. In addition, we find C. albicans Pus7 modifies tRNA residues, but does not modify a number of other S. cerevisiae Pus7 substrates. Our data suggests C. albicans Pus7 is important for fungal vigour and may play distinct biological roles than those ascribed to S. cerevisiae Pus7.
RNA 可以被超过 100 种不同的方式修饰，这些修饰对功能至关重要。假尿嘧啶合酶催化假尿嘧啶化，这是最普遍的 RNA 修饰之一。假尿嘧啶合酶 7 在酿酒酵母中修饰多种底物，包括 tRNA、rRNA、snRNA 和 mRNA，但其他芽殖酵母 Pus7 同源物的底物尚不清楚。我们使用 CRISPR 介导的基因组编辑来破坏白色念珠菌 PUS7，并发现缺失会导致 rRNA 加工缺陷和细胞表面疏水性降低。此外，C. albicans Pus7 的缺失会导致温度敏感性、菌丝形成缺陷、对抗真菌药物的敏感性改变以及在蜡蛾模型中的毒力降低。此外，我们发现 C. albicans Pus7 修饰 tRNA 残基，但不修饰许多其他 S. cerevisiae Pus7 底物。我们的数据表明，C. albicans Pus7 对真菌活力很重要，它可能发挥着与 S. cerevisiae Pus7 不同的生物学作用。
