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

TitleGenome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development.
Publication TypeJournal Article
Year of Publication2018
AuthorsPainter, HJ, Chung, NChristophe, Sebastian, A, Albert, I, Storey, JD, Llinás, M
JournalNat Commun
Volume9
Issue1
Pagination2656
Date Published2018 Jul 09
ISSN2041-1723
KeywordsErythrocytes, Gene Expression Profiling, Gene Ontology, Genes, Protozoan, Genome, Protozoan, Humans, Malaria, Falciparum, Plasmodium falciparum, RNA, Messenger, RNA, Protozoan, Transcription, Genetic
Abstract

<p>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.</p>

DOI10.1038/s41467-018-04966-3
Alternate JournalNat Commun
PubMed ID29985403
PubMed Central IDPMC6037754
Grant ListR21 AI133379 / AI / NIAID NIH HHS / United States