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

Heather Jill Painter Ponton, Neo Christopher Chung, Aswathy Sebastian, Istvan Albert, John D. Storey, Manuel Llinas

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number2656
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

genome
Plasmodium falciparum
blood
Blood
Genes
Genome
Messenger RNA
cycles
Transcription
parasites
pyrimidines
deoxyribonucleic acid
stabilization
time measurement
Salvaging
Nucleotide Motifs
Falciparum Malaria
DNA sequences
Gene Expression Profiling
Statistical Models

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Painter Ponton, Heather Jill ; Chung, Neo Christopher ; Sebastian, Aswathy ; Albert, Istvan ; Storey, John D. ; Llinas, Manuel. / Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development. In: Nature communications. 2018 ; Vol. 9, No. 1.
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abstract = "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.",
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Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development. / Painter Ponton, Heather Jill; Chung, Neo Christopher; Sebastian, Aswathy; Albert, Istvan; Storey, John D.; Llinas, Manuel.

In: Nature communications, Vol. 9, No. 1, 2656, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Albert, Istvan

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AU - Llinas, Manuel

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