Francisco Alejandro Lagunas-Rangel1. 1. Department of Surgical Sciences, Uppsala University, Husargatan 3, BMC Box 593, 75124, Uppsala, Sweden. francisco.lagunas@neuro.uu.se.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The inhibition of the rRNA transcription machinery in parasites might be a new therapeutic strategy against these microorganisms.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The inhibition of the rRNA transcription machinery in parasites might be a new therapeutic strategy against these microorganisms.
Authors: Francisco Alejandro Lagunas-Rangel; María Luisa Bazán-Tejeda; Rosa María Bermúdez-Cruz Journal: Acta Trop Date: 2021-02-25 Impact factor: 3.112