In vivo and in vitro genome-wide profiling of RNA secondary structures reveals key regulatory features in Plasmodium falciparum

It is widely accepted that the RNA structure has important roles in biological behavior, such as polyadenylation, splicing, and catalytic functions. Dynamic RNA structural changes are able to regulate gene expression program and can be used as an extremely specific and subtle mechanism for cellular processes. However, the nature of most RNA secondary structures in Plasmodium falciparum are not known. In order to investigate the single-nucleotide resolution and genome-wide RNA secondary structural features in P. falciparum, here we apply a novel high-throughput method utilizing the chemical modification of RNA structures to assess RNA structures. Structure data from parasites is in an excellent agreement with known 18S ribosomal RNA secondary structures of the P. falciparum and can help to predict the RNA secondary structure in vivo of totally 3,396 transcripts in the ring stage and trophozoite stage developmental cycles. By parallel analysis of RNA structures in vivo and in vitro during the Plasmodium parasites ring stage and trophozoite stage intra-erythrocytic developmental cycle, we identified some key regulatory features. Recent studies establish the RNA structure as a pervasive and fundamental regulator of gene expression. Our study adds to the accumulating evidence that there has a critical connection between RNA secondary structure and mRNA abundance during the complex biological program of P. falciparum. This work offers a huge framework and more important information for further investigate the interactions between RNA secondary structure and the complex biological program and the structural basis of P. falciparum. And our RNA secondary structurome have potential use and important implications for the discovery of RNA structural elements important for parasite infection and understanding of host-parasite interaction and parasite-surroundings.