Department of Surgical Sciences, Uppsala University, Husargatan 3, BMC Box 593, 75124, Uppsala, Sweden.
Acta Parasitol. 2022 Dec;67(4):1788-1799. doi: 10.1007/s11686-022-00612-7. Epub 2022 Aug 27.
Ribosome biogenesis is a key process in all living organisms, energetically expensive and tightly regulated. Currently, little is known about the components of the ribosomal RNA (rRNA) transcription machinery that are present in intestinal parasites, such as Giardia duodenalis, Cryptosporidium parvum, and Entamoeba histolytica. Thus, in the present work, an analysis was carried out looking for the components of the rRNA transcription machinery that are conserved in intestinal parasites and if these could be used to design new treatment strategies.
The different components of the rRNA transcription machinery were searched in the studied parasites with the NCBI BLAST tool in the EuPathDB Bioinformatics Resource Center database. The sequences of the RRN3 and POLR1F orthologs were aligned and important regions identified. Subsequently, three-dimensional models were built with different bioinformatic tools and a structural analysis was performed.
Among the protozoa examined, C. parvum is the parasite with the fewest identifiable components of the rRNA transcription machinery. TBP, RRN3, POLR1A, POLR1B, POLR1C, POLR1D, POLR1F, POLR1H, POLR2E, POLR2F and POLR2H subunits were identified in all species studied. Furthermore, the interaction regions between RRN3 and POLR1F were found to be conserved and could be used to design drugs that inhibit rRNA transcription in the parasites studied.
The inhibition of the rRNA transcription machinery in parasites might be a new therapeutic strategy against these microorganisms.
核糖体生物发生是所有生物的关键过程，能量消耗大且受到严格调控。目前，对于存在于肠道寄生虫（如十二指肠贾第鞭毛虫、微小隐孢子虫和溶组织内阿米巴）中的核糖体 RNA（rRNA）转录机制的组成部分知之甚少。因此，本研究旨在分析肠道寄生虫中保守的 rRNA 转录机制的组成部分，以及这些组成部分是否可用于设计新的治疗策略。
使用 NCBI BLAST 工具在 EuPathDB 生物信息学资源中心数据库中搜索研究寄生虫中的 rRNA 转录机制的不同组成部分。对 RRN3 和 POLR1F 直系同源物的序列进行比对，并确定重要区域。随后，使用不同的生物信息学工具构建三维模型并进行结构分析。
在所检查的原生动物中，微小隐孢子虫是 rRNA 转录机制可识别组成部分最少的寄生虫。在所有研究的物种中都鉴定出 TBP、RRN3、POLR1A、POLR1B、POLR1C、POLR1D、POLR1F、POLR1H、POLR2E、POLR2F 和 POLR2H 亚基。此外，还发现 RRN3 和 POLR1F 之间的相互作用区域保守，可用于设计抑制研究寄生虫中 rRNA 转录的药物。
抑制寄生虫的 rRNA 转录机制可能是针对这些微生物的新治疗策略。
