Browsing by Author "Gedara, Sanjaya Aththawala"

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    Widespread release of translational repression across Plasmodium’s host-to-vector transmission event
    (Public Library of Science, 2025-01-08) Rios, Kelly T.; McGee, James P.; Sebastian, Aswathy; Gedara, Sanjaya Aththawala; Moritz, Robert L.; Feric, Marina; Absalon, Sabrina; Swearingen, Kristian E.; Lindner, Scott E.; Pharmacology and Toxicology, School of Medicine
    Malaria parasites must respond quickly to environmental changes, including during their transmission between mammalian and mosquito hosts. Therefore, female gametocytes proactively produce and translationally repress mRNAs that encode essential proteins that the zygote requires to establish a new infection. While the release of translational repression of individual mRNAs has been documented, the details of the global release of translational repression have not. Moreover, changes in the spatial arrangement and composition of the DOZI/CITH/ALBA complex that contribute to translational control are also not known. Therefore, we have conducted the first quantitative, comparative transcriptomics and DIA-MS proteomics of Plasmodium parasites across the host-to-vector transmission event to document the global release of translational repression. Using female gametocytes and zygotes of P. yoelii, we found that ~200 transcripts are released for translation soon after fertilization, including those encoding essential functions. Moreover, we identified that many transcripts remain repressed beyond this point. TurboID-based proximity proteomics of the DOZI/CITH/ALBA regulatory complex revealed substantial spatial and/or compositional changes across this transmission event, which are consistent with recent, paradigm-shifting models of translational control. Together, these data provide a model for the essential translational control mechanisms that promote Plasmodium's efficient transmission from mammalian host to mosquito vector.