ArticleMalaria journal2022
Functional characterization of 5' UTR cis-acting sequence elements that modulate translational efficiency in Plasmodium falciparum and humans.
Article in Malaria journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Highly efficient intranasal H5N1 vaccine based on a safe vesicular stomatitis virus (VSV) vector.Signal transduction and targeted therapy · 2026Article
- Enhancing mRNA translation efficiency with discriminative and generative artificial intelligence by optimizing 5' UTR sequences.iScience · 2025Article
- Post-transcriptional regulation and subcellular localization of G-protein γ7 subunit: implications for striatal function and behavioral responses to cocaine.Frontiers in neuroanatomy · 2024Article
- Precise genome editing of the Kozak sequence enables bidirectional and quantitative modulation of protein translation to anticipated levels without affecting transcription.Nucleic acids research · 2023Article
- Transcriptomic complexity of the human malaria parasite Plasmodium falciparum revealed by long-read sequencing.PloS one · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe eukaryotic parasite Plasmodium falciparum causes millions of malarial infections annually while drug resistance to common anti-malarials is further confounding eradication efforts. Translation is an attractive therapeutic target that will benefit from a deeper mechanistic understanding. As the rate limiting step of translation, initiation is a primary driver of translational efficiency. It is a complex process regulated by both cis and trans acting factors, providing numerous potential targets. Relative to model organisms and humans, P. falciparum mRNAs feature unusual 5' untranslated regions suggesting cis-acting sequence complexity in this parasite may act to tune levels of protein synthesis through their effects on translational efficiency.
methodsHere, in vitro translation is deployed to compare the role of cis-acting regulatory sequences in P. falciparum and humans. Using parasite mRNAs with high or low translational efficiency, the presence, position, and termination status of upstream "AUG"s, in addition to the base composition of the 5' untranslated regions, were characterized.
resultsThe density of upstream "AUG"s differed significantly among the most and least efficiently translated genes in P. falciparum, as did the average "GC" content of the 5' untranslated regions. Using exemplars from highly translated and poorly translated mRNAs, multiple putative upstream elements were interrogated for impact on translational efficiency. Upstream "AUG"s were found to repress translation to varying degrees, depending on their position and context, while combinations of upstream "AUG"s had non-additive effects. The base composition of the 5' untranslated regions also impacted translation, but to a lesser degree. Surprisingly, the effects of cis-acting sequences were remarkably conserved between P. falciparum and humans.
conclusionsWhile translational regulation is inherently complex, this work contributes toward a more comprehensive understanding of parasite and human translational regulation by examining the impact of discrete cis-acting features, acting alone or in context.
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