Abstract
Messenger RNA polyadenylation is a universal aspect of gene expression in eukaryotes. In well-established model organisms, this process is mediated by a conserved complex of 15–20 subunits. To better understand this process in apicomplexans, a group of unicellular parasites that causes serious disease in humans and livestock, a computational and high throughput sequencing study of the polyadenylation complex and poly(A) sites in several species was conducted. BLAST-based searches for orthologs of the human polyadenylation complex yielded clear matches to only two—poly(A) polymerase and CPSF73—of the 19 proteins used as queries in this analysis. As the human subunits that recognize the AAUAAA polyadenylation signal (PAS) were not immediately obvious, a computational analysis of sequences adjacent to experimentally-determined apicomplexan poly(A) sites was conducted. The results of this study showed that there exists in apicomplexans an A-rich region that corresponds in position to the AAUAAA PAS. The set of experimentally-determined sites in one species, Sarcocystis neurona, was further analyzed to evaluate the extent and significance of alternative poly(A) site choice in this organism. The results showed that almost 80% of S. neurona genes possess more than one poly(A) site, and that more than 780 sites showed differential usage in the two developmental stages–extracellular merozoites and intracellular schizonts–studied. These sites affected more than 450 genes, and included a disproportionate number of genes that encode membrane transporters and ribosomal proteins. Taken together, these results reveal that apicomplexan species seem to possess a poly(A) signal analogous to AAUAAA even though genes that may encode obvious counterparts of the AAUAAA-recognizing proteins are absent in these organisms. They also indicate that, as is the case in other eukaryotes, alternative polyadenylation is a widespread phenomenon in S. neurona that has the potential to impact growth and development.
Highlights
A conclusion drawn by the authors of a study of the genome of G. lamblia is provocative [40]; these authors noted that the genome of this organism seems to possess genes encoding only three of the subunits (CPSF73, CPSF30, and poly(A) polymerase (PAP)) seen in the mammalian complex
The three apicomplexan proteins show significant similarity in the CCCH motifs, and in the YTH domain. This arrangement is confirmed by mapping of RNA-Seq reads S. neurona. These results show that the parts of the putative S. neurona CPSF30 gene that encode the zinc finger arrays and the YTH domains may be connected by individual rRNA-Seq reads, providing support for the hypothesis that, as is the case in plants, these two domains are present in a single polypeptide
PAP is coordinated with the cleaved pre-mRNA by the CPSF subcomplex, and several protein-protein interactions between CPSF subunits and PAP have been reported; these do not include direct contacts between CPSF73 and PAP
Summary
The consensus picture of polyadenylation and its impact on gene expression comes largely from studies conducted in a small number of systems–various animals, yeast, and higher plants This consensus would seem to be broadly applicable; for example, trypanosomes possesses a similar complement of polyadenylation complex subunits, and these exist in analogous subcomplexes (CPSF, for example) and are important for polyadenylation and organismal survival [15,16,17,18]. A subunit of the core poly(A) complex is a target of a novel antiprotozoal compound in T. gondii [30] and P. falciparum [31] Given the latter reports, further study of the process of polyadenylation in these two organisms, and in other apicomplexans of agricultural importance, is needed. They suggest the occurrence of changes in poly(A) site choice during asexual development of S. neurona
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
