Poster abstracts

Poster number 36 submitted by Cassandra Catacalos

Polyadenylation site choice correlates with epitranscriptomic mark, N6-methyladenosine (m6A), in Plasmodium falciparum

Cassandra Catacalos (Department of Biological Sciences, University of North Carolina, Charlotte, NC, USA), Manohar Chakrabarti, Arthur Hunt (Department of Plant and Soil Sciences, University of Kentucky, Lexington, KY, USA), David Zhu, Kate Meyer (Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA), Robert Reid (Department of Bioinformatics, University of North Carolina, Charlotte, NC, USA), Kausik Chakrabarti (Department of Biological Sciences, University of North Carolina, Charlotte, NC, USA)

The recent discoveries of post-transcriptional modifications of mRNA have opened the possibility to understand a previously underappreciated regulatory layer involved in biological processes. Among all RNA modifications, N6-methyladenosine (m6A) is the most abundant epitranscriptomic mark and regulates numerous cellular processes. Functional roles of this mark are carried out by m6A binding proteins, “readers”, which bind m6A residues and contribute to various aspects of mRNA regulation. Although the function of m6A in mRNA stability and translation has been well established, the implication of m6A in the control of mRNA 3’ end processing, remains obscure. Polyadenylation is the post-transcriptional addition of multiple adenine (A) nucleotides to the tail of a mRNA transcript, which requires recognition of a sequence element, AAUAAA, for efficient cleavage and poly(A) tail addition. However, an unresolved question remains in eukaryotic biology is how polyadenylation machinery is able to distinguish ‘bona-fide’ polyadenylation signals from the multiple look-alikes interspersed along the 3' UTRs? This is particularly intriguing in the Apicomplexan family with exceedingly A/T-rich genomes, such as the malaria pathogen Plasmodium falciparum. This pathogen’s gene expression varies hourly during its 48 hour human intraerythrocytic developmental cycle (IDC). We found that its genome harbors a cleavage and polyadenylation specificity factor, CPSF30, which possesses a characteristic reader domain. The strategic locations of m6A marks in Plasmodium mRNAs, nearby poly(A) sites, lends itself to the hypothesis that m6A may be a determinant of 3’ end processing in P. falciparum. We will present data from our global identification of m6A sites in P. falciparum, transcriptome-wide characterization of 3’ end processing events and molecular analysis of Plasmodium polyadenylation machinery that links epitranscriptomics 3’-end signatures in Plasmodium falciparum.

Keywords: Plasmodium, m6A, polyadenylation