The Plasmodium NOT1-G paralogue is an essential regulator of sexual stage maturation and parasite transmission.

Autor: Hart KJ; Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America., Power BJ; Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America., Rios KT; Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America., Sebastian A; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, United States of America., Lindner SE; Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2021 Oct 21; Vol. 19 (10), pp. e3001434. Date of Electronic Publication: 2021 Oct 21 (Print Publication: 2021).
DOI: 10.1371/journal.pbio.3001434
Abstrakt: Productive transmission of malaria parasites hinges upon the execution of key transcriptional and posttranscriptional regulatory events. While much is now known about how specific transcription factors activate or repress sexual commitment programs, far less is known about the production of a preferred mRNA homeostasis following commitment and through the host-to-vector transmission event. Here, we show that in Plasmodium parasites, the NOT1 scaffold protein of the CAF1/CCR4/Not complex is duplicated, and one paralogue is dedicated for essential transmission functions. Moreover, this NOT1-G paralogue is central to the sex-specific functions previously associated with its interacting partners, as deletion of not1-g in Plasmodium yoelii leads to a comparable or complete arrest phenotype for both male and female parasites. We show that, consistent with its role in other eukaryotes, PyNOT1-G localizes to cytosolic puncta throughout much of the Plasmodium life cycle. PyNOT1-G is essential to both the complete maturation of male gametes and to the continued development of the fertilized zygote originating from female parasites. Comparative transcriptomics of wild-type and pynot1-g- parasites shows that loss of PyNOT1-G leads to transcript dysregulation preceding and during gametocytogenesis and shows that PyNOT1-G acts to preserve mRNAs that are critical to sexual and early mosquito stage development. Finally, we demonstrate that the tristetraprolin (TTP)-binding domain, which acts as the typical organization platform for RNA decay (TTP) and RNA preservation (ELAV/HuR) factors is dispensable for PyNOT1-G's essential blood stage functions but impacts host-to-vector transmission. Together, we conclude that a NOT1-G paralogue in Plasmodium fulfills the complex transmission requirements of both male and female parasites.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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