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mRNA Polyadenylation Machineries in Intestinal Protozoan Parasites
Juan David Ospina-Villa1, Brisna Joana Tovar-Ayona2, César López-Camarillo3
1Independent Researcher, Transversal 27A Sur # 42-14, C.P. 055421, Envigado, Antioquia, Colombia.
Abstract:
In humans, mRNA polyadenylation involves the participation of about 20 factors in four main complexes that recognize specific RNA sequences. Notably, CFIm25, CPSF73, and PAP have essential roles for poly(A) site selection, mRNA cleavage, and adenosine residues polymerization. Besides the relevance of polyadenylation for gene expression, information is scarce in intestinal protozoan parasites that threaten human health. To better understand polyadenylation in Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum, which represent leading causes of diarrhea worldwide, genomes were screened for orthologs of human factors. Results showed that Entamoeba histolytica and C. parvum have 16 and 12 proteins out of the 19 human proteins used as queries, respectively, while G. lamblia seems to have the smallest polyadenylation machinery with only six factors. Remarkably, CPSF30, CPSF73, CstF77, PABP2, and PAP, which were found in all parasites, could represent the core polyadenylation machinery. Multiple genes were detected for several proteins in Entamoeba, while gene redundancy is lower in Giardia and Cryptosporidium. Congruently with their relevance in the polyadenylation process, CPSF73 and PAP are present in all parasites, and CFIm25 is only missing in Giardia. They conserve the functional domains and predicted folding of human proteins, suggesting they may have the same roles in polyadenylation.
Insights
Investigating mRNA polyadenylation machinery in parasitic protozoa reveals Entamoeba histolytica and Cryptosporidium parvum possess substantial components, while Giardia lamblia has a minimal set, suggesting conserved functions.
Area of Science:
- Molecular Biology
- Parasitology
- Genomics
Background:
- mRNA polyadenylation is crucial for gene expression, involving ~20 human factors in four complexes.
- Key factors include CFIm25, CPSF73, and PAP, essential for poly(A) site selection, cleavage, and polymerization.
- Polyadenylation mechanisms in key intestinal protozoan parasites remain poorly understood.
Purpose of the Study:
- To investigate the polyadenylation machinery in Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum.
- To identify conserved and divergent factors involved in mRNA processing in these human pathogens.
- To infer potential functional roles of identified factors based on human orthologs.
Main Methods:
- Genomic screening for orthologs of human polyadenylation factors.
- Comparative analysis of protein factor content across parasite species.
- Examination of gene redundancy and conservation of functional domains.
Main Results:
- Entamoeba histolytica and Cryptosporidium parvum possess 16 and 12 human orthologs, respectively.
- Giardia lamblia appears to have a minimal machinery with only six factors.
- CPSF30, CPSF73, CstF77, PABP2, and PAP are conserved across all studied parasites, potentially forming a core machinery.
- CPSF73 and PAP are universally present; CFIm25 is absent in Giardia.
- Identified parasite proteins conserve functional domains and folding, suggesting conserved roles.
Conclusions:
- Parasitic protozoa exhibit significant variation in their mRNA polyadenylation machinery.
- A core set of polyadenylation factors is conserved across Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum.
- Conserved factors likely perform similar functions to their human counterparts, despite evolutionary divergence.
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