Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development

• Published in: Nature communications Vol. 9; no. 1; pp. 2656 - 12
• Main Authors: Painter, Heather J, Chung, Neo Christopher, Sebastian, Aswathy, Albert, Istvan, Storey, John D, Llinás, Manuel
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 09.07.2018; Nature Publishing Group UK; Nature Portfolio
• Subjects: Abundance; Blood; Deoxyribonucleic acid; Developmental stages; DNA; Erythrocytes; Erythrocytes - parasitology; Gene expression; Gene Expression Profiling; Gene Ontology; Genes, Protozoan - genetics; Genome, Protozoan - genetics; Genomes; Humans; Malaria; Malaria, Falciparum - parasitology; Mathematical models; Nucleotide sequence; Parasites; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - physiology; Regulatory sequences; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Protozoan - genetics; RNA, Protozoan - metabolism; Salvage; Statistical models; Synthesis; Transcription; Transcription, Genetic; Transcriptomes; Transcriptomics; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04966-3

Genome-wide analysis of transcription in the malaria parasite Plasmodium falciparum has revealed robust variation in steady-state mRNA abundance throughout the 48-h intraerythrocytic developmental cycle (IDC), suggesting that this process is highly dynamic and tightly regulated. Here, we utilize rapid 4-thiouracil (4-TU) incorporation via pyrimidine salvage to specifically label, capture, and quantify newly-synthesized RNA transcripts at every hour throughout the IDC. This high-resolution global analysis of the transcriptome captures the timing and rate of transcription for each newly synthesized mRNA in vivo, revealing active transcription throughout all IDC stages. Using a statistical model to predict the mRNA dynamics contributing to the total mRNA abundance at each timepoint, we find varying degrees of transcription and stabilization for each mRNA corresponding to developmental transitions. Finally, our results provide new insight into co-regulation of mRNAs throughout the IDC through regulatory DNA sequence motifs, thereby expanding our understanding of P. falciparum mRNA dynamics.