Liu Congshan, Cao Jianping, Zhang Haobing, Yin Jianhai
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, China.
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, China.
Infect Genet Evol. 2021 Dec;96:105124. doi: 10.1016/j.meegid.2021.105124. Epub 2021 Oct 26.
RNA modifications, as one of epigenetic mechanisms, are important and conserved mechanisms for maintaining the homeostasis of organisms. Little is known about RNA modifications in Echinococcus granulosus, an obligate parasite that inhabits mammals and gives rise to a huge public health and economic impact. Here, we focused on the RNA modification characteristics of E. granulosus for the first time by using mass spectrometry (UPLC-MS/MS) to qualitatively and quantitatively analyze 47 types of RNA modifications in E. granulosus total RNA. Furthermore, the E. granulosus homologs of writer enzymes preforming RNA modifications were identified, and their gene expression pattern at different developmental stages were analyzed by bioinformatics analysis. Finally, 23 types of RNA modifications were found in E. granulosus cysts total RNA, of which mA, Ψ and mC are the most abundant. The homologs of writer enzymes involved in these modifications were identified in the E. granulosus genome, with the dynamic gene expression during the different parasitic developmental stages. This work confirms that E. granulosus retains the conserved RNA modification mechanism during evolution, suggesting the important role of RNA modification in regulating its development and parasitic process. Moreover, the differences of amino acid sequences of RNA modification writer enzymes between parasite and host make it possible to use these enzymes as the candidate drug targets in the follow-up in-depth researches.
RNA修饰作为表观遗传机制之一,是维持生物体稳态的重要且保守的机制。对于细粒棘球绦虫这种专性寄生虫的RNA修饰,人们了解甚少,它寄生于哺乳动物体内,对公共卫生和经济造成了巨大影响。在此,我们首次聚焦于细粒棘球绦虫的RNA修饰特征,利用质谱法(超高效液相色谱-串联质谱法,UPLC-MS/MS)对细粒棘球绦虫总RNA中的47种RNA修饰进行定性和定量分析。此外,鉴定了执行RNA修饰的书写酶的细粒棘球绦虫同源物,并通过生物信息学分析对其在不同发育阶段的基因表达模式进行了分析。最后,在细粒棘球绦虫囊肿总RNA中发现了23种RNA修饰,其中N6-甲基腺苷(mA)、假尿苷(Ψ)和5-甲基胞嘧啶(mC)最为丰富。在细粒棘球绦虫基因组中鉴定出了参与这些修饰的书写酶的同源物,它们在不同的寄生发育阶段具有动态基因表达。这项工作证实细粒棘球绦虫在进化过程中保留了保守的RNA修饰机制,表明RNA修饰在调节其发育和寄生过程中具有重要作用。此外,寄生虫与宿主之间RNA修饰书写酶氨基酸序列的差异使得这些酶有可能在后续深入研究中作为候选药物靶点。