Regional Centre for Biotechnology, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad 121001, India.
Regional Centre for Biotechnology, 3rd Milestone Gurgaon-Faridabad Expressway, Faridabad 121001, India.
Mol Aspects Med. 2021 Oct;81:101017. doi: 10.1016/j.mam.2021.101017. Epub 2021 Sep 5.
Host-pathogen interactions at the molecular level are the key to fungal pathogenesis. Fungal pathogens utilize several mechanisms such as adhesion, invasion, phenotype switching and metabolic adaptations, to survive in the host environment and respond. Post-transcriptional and translational regulations have emerged as key regulatory mechanisms ensuring the virulence and survival of fungal pathogens. Through these regulations, fungal pathogens effectively alter their protein pool, respond to various stress, and undergo morphogenesis, leading to efficient and comprehensive changes in fungal physiology. The regulation of virulence through post-transcriptional and translational regulatory mechanisms is mediated through mRNA elements (cis factors) or effector molecules (trans factors). The untranslated regions upstream and downstream of the mRNA, as well as various RNA-binding proteins involved in translation initiation or circularization of the mRNA, play pivotal roles in the regulation of morphology and virulence by influencing protein synthesis, protein isoforms, and mRNA stability. Therefore, post-transcriptional and translational mechanisms regulating the morphology, virulence and drug-resistance processes in fungal pathogens can be the target for new therapeutics. With improved "omics" technologies, these regulatory mechanisms are increasingly coming to the forefront of basic biology and drug discovery. This review aims to discuss various modes of post-transcriptional and translation regulations, and how these mechanisms exert influence in the virulence and morphogenesis of fungal pathogens.
宿主-病原体在分子水平上的相互作用是真菌发病机制的关键。真菌病原体利用几种机制,如黏附、入侵、表型转换和代谢适应,在宿主环境中生存并作出反应。转录后和翻译后调控已成为确保真菌病原体毒力和存活的关键调节机制。通过这些调节,真菌病原体能够有效地改变其蛋白质库,对各种应激作出反应,并进行形态发生,从而导致真菌生理学的有效和全面变化。通过转录后和翻译后调节机制来调节毒力是通过 mRNA 元件(顺式因子)或效应分子(反式因子)来介导的。mRNA 上下游的非翻译区以及涉及翻译起始或 mRNA 环化的各种 RNA 结合蛋白,通过影响蛋白质合成、蛋白质同工型和 mRNA 稳定性,在调节形态和毒力方面发挥着重要作用。因此,调节真菌病原体形态、毒力和耐药性过程的转录后和翻译机制可以成为新疗法的靶点。随着“组学”技术的不断提高,这些调节机制越来越成为基础生物学和药物发现的前沿领域。本文旨在讨论各种转录后和翻译调控模式,以及这些机制如何在真菌病原体的毒力和形态发生中发挥作用。