ALBA4 modulates its stage‐specific interactions and specific mRNA fates during <i>Plasmodium yoelii</i> growth and transmission

Munoz, Elyse E.; Hart, Kevin J.; Walker, Michael P.; Kennedy, Mark; Shipley, Mackenzie M.; Lindner, Scott E.

doi:10.1111/mmi.13762

Cited by 43 publications

(86 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, in both P. yoelii and P. falciparum , CelTOS, GEST and SPELD were not detected or were only weakly expressed in oocyst sporozoites, but were among the most abundant proteins in salivary gland sporozoites (Table 2, Table S1). Moreover, the presence/absence of cellular regulators such as specific ApiAP2s, histone modifiers, RNA-binding proteins and other proteins (Table S1) agree with previous reports describing how these types of regulation may be used by the sporozoite 32, 40, 48 .…”

Section: Resultssupporting

confidence: 90%

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Lindner

Swearingen

Shears

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

22 Introduction: 41Malaria remains one of the great global health problems today, taking a large toll on people in the 42 tropics and subtropics. This disease, caused by Plasmodium parasites, affects over 200 million people 43 annually and kills over 400,000 (WHO World Malaria Report 2018). While a protein-based subunit 44 vaccine (RTS,S) has recently been licensed and is being used for pilot implementation in three Saharan African countries, its protection has been limited and relatively short-lived in clinical trials 1 . 46 Identifying and fully testing an effective and long-lasting malaria vaccine remains a chief goal that has 47 yet to be achieved. Accomplishing this will require greater knowledge of the basic biology of the pre-48 erythrocytic sporozoite and liver stage parasites. Promising new whole-parasite vaccine candidates, 49 based upon the sporozoite form of the parasite, are on the horizon and hopefully will meet these needs 50 2 . 51Plasmodium parasites are transmitted between hosts by an infected female Anopheles mosquito 52 (reviewed in 3 ). Following uptake of male and female gametocytes by the mosquito during a blood meal 53 of an infected host, these parasites activate into male and female gametes in the midgut, fuse into a 54 zygote, and develop into a motile ookinete, which burrows through the midgut wall and establishes an 55 oocyst under the basal lamina. Within the oocyst, the parasite undergoes sporogony to produce up to 56 five thousand oocyst sporozoites 4 . These oocyst sporozoites are weakly infectious if injected directly 57 into a naïve mammalian host 5 , but become highly infectious following proteolytic rupture of the oocyst 58 wall and transit through the mosquito hemocoel. Sporozoites further gain infectivity after invasion of 59 the salivary glands 5,6 . Interestingly, the gain of infectivity for the mammalian host is concomitant with a 60 loss of infectivity for the salivary glands. Within the glands, the sporozoites await transmission as 61 salivary gland sporozoites, which occurs when the mosquito takes its next blood meal. Infection of a 62 host begins with the injection of salivary gland sporozoites into the skin. Following this, sporozoites exit 63 the bite site in the skin, locate and enter the vasculature, and passively travel to the liver, where 64 sporozoites can productively infect hepatocytes, which initiates the life cycle progression in the 65 mammalian host 7 . Moreover, because relatively few sporozoites are injected during a mosquito bite 8 , 66 this transmission event bottleneck has been the focus of intervention efforts using drugs, subunit 67 vaccines, and attenuated whole parasite vaccines 2 . 68Fundamental studies of sporozoite biology have informed efforts to inhibit and/or arrest the parasite 69 during development. To date, genetically-attenuated parasite (GAP) vaccine candidates were generated 70 by the deletion of genes whose transcripts are Up-regulated in Infective (Salivary Gland) Sporozoites 71 (UIS). The UIS gene family was originally determi...

show abstract

Section: Resultssupporting

confidence: 90%

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Lindner

Swearingen

Shears

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…As our recent RNA-sequencing data from Plasmodium yoelii shows that all four genes are expressed in asexual blood stages and in gametocytes (4), we sought to determine if any of the CCR4 domain-containing proteins played an important, stage-specific role in the parasite life cycle. To this end, we replaced their coding sequences with a GFP-expression cassette and a human dihydrofolate reductase (HsDHFR)-expression cassette via double homologous recombination in the Plasmodium yoelii 17XNL strain (Figures S2CDEF).…”

Section: Resultsmentioning

confidence: 99%

“…Recent work has shown that the parasite requires tight transcriptional and translational control to navigate these complex transmission events (4–8). Despite the complex events required for the effective transmission of the parasite, Plasmodium has only one known, expanded family of specific transcription factors, the ApiAP2 proteins (reviewed in (9)).…”

Section: Introductionmentioning

confidence: 99%

Plasmodium male gametocyte development and transmission are critically regulated by general and transmission-specific members of the CAF1/CCR4/NOT complex

Hart

Oberstaller

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

19With relatively few known specific transcription factors to control the abundance of specific 20 mRNAs, Plasmodium parasites also regulate the stability and turnover of transcripts to provide 21 more comprehensive gene regulation. Plasmodium transmission stages impose translational 22 38 39 3 AUTHOR SUMMARY 40 Malaria is a disease caused by Plasmodium parasites, which are transmitted during an 41 infectious blood meal by anopheline mosquitoes. Transmission of the sexual stages of the 42 parasite to mosquitoes requires the proper regulation of specific mRNAs. While much work has 43 been done to characterize regulation of mRNAs in female gametocytes, little has been done to 44 assess this regulation in male gametocytes. Here, we demonstrate that PyCCR4-1, a member of 45 the CAF1/CCR4/NOT RNA metabolic complex, acts upon transcripts both directly and indirectly 46 in both male and female parasites, and results in a reduction of male gametocytemia. In 47

show abstract

“…This is supported by the abundant presence RNA-binding proteins [13, 14] and RNA degradation components [15] in the P. falciparum genome. The includePfALBA1 [16], PfCAF1 [17] in P. falciparum and PyCCR4 [18], PyALBA4 [19] in rodent-specific P.yoelii all of which functions were directly implicated in regulation of transcript levels. Moreover, variability of mRNA half-lives across the IDC observed by several experimental approaches also suggested a significant contribution of mRNA decay in regulation of gene expression in malaria parasites [20].…”

Section: Introductionmentioning

confidence: 99%

Antagonistic roles of NOT1 paralogues in the timing of gene expression inPlasmodium falciparum

Liu

Rai

Zhu

et al. 2020

Preprint

View full text Add to dashboard Cite

18NOT1 is the scaffold of the CCR4-NOT complex, a highly conserved multi-protein complex that 19 regulates gene expression in eukaryotes. As opposed to most eukaryotes in which NO1 is 20 encoded by a single gene, malaria parasites, Plasmodium falciparum, carry two NOT1 21 paralogues, PfNOT1.1 and PfNOT1.2. Here we showed that the two PfNOT1 proteins function as 22 3 38 possess an additional copy of PfNOT1 in the parasite. Here we described antagonistic regulatory 39 functions of two PfNOT1 paralogues in gene expression during the 48-hour intraerythrocytic 40 developmental cycle. We also reported that their regulatory functions are predominantly post-41 transcriptional and proposed a model in which distinct PfCCR4-NOT complexes defined by 42 mutually exclusive PfNOT1 scaffolds differentially regulate PfCAF1 function in mRNA decay. This 43 study highlights the importance of post-transcriptional regulation in P. falciparum and provides 44 novel insights into mechanisms of gene regulation in this organism. The unique presence of two 45 PfNOT1 paralogues may also open avenues for the development of new drug targets for anti-46 malarial control. 47 4 58 expression [4]. Hence, gene expression is highly regulated across the IDC at multiple levels, 59 ranging from epigenetic regulation, transcription and post-transcriptional regulation. 60 While the basic mechanism of eukaryotic transcription and general transcription components 61 are conserved in P. falciparum [5, 6], most TBP-associated factors (TAF) are absent [6] and only 62 a third of the expected number of canonical eukaryotic transcription activating proteins (TAP) 63 were predicted in the parasite genome [7]. The presence of 27 Apicomplexan-specific 64 transcription factors, ApiAP2, may compensate for the reduction in the number of conventional 65 transcription components [8, 9]. These 27 ApiAP2 proteins display distinct expression profiles 66 covering the entire IDC [8] and their recognition motifs are located in the promoter regions of 67 most genes whose expression profiles are positively correlated to expression of the 68 corresponding ApiAP2 gene [9]. In addition to transcriptional initiation, there is mounting 69 evidence that multiple processes of post-transcriptional regulation are also critical for 70 regulation of mRNA abundance through the P. falciparum IDC [10-12]. This is supported by the 71 abundant presence RNA-binding proteins [13, 14] and RNA degradation components [15] in the 72 P. falciparum genome. The includePfALBA1 [16], PfCAF1 [17] in P. falciparum and PyCCR4 [18], 73 PyALBA4 [19] in rodent-specific P.yoelii all of which functions were directly implicated in 74 regulation of transcript levels. Moreover, variability of mRNA half-lives across the IDC observed 75 by several experimental approaches also suggested a significant contribution of mRNA decay in 76 regulation of gene expression in malaria parasites [20]. Taken together, both transcriptional 77 regulation and post-transcriptional regulation play critical roles in modulating transcr...

show abstract

ALBA4 modulates its stage‐specific interactions and specific mRNA fates during Plasmodium yoelii growth and transmission

Cited by 43 publications

References 64 publications

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Extensive Transcriptional and Translational Regulation Occur During the Maturation of Malaria Parasite Sporozoites

Plasmodium male gametocyte development and transmission are critically regulated by general and transmission-specific members of the CAF1/CCR4/NOT complex

Antagonistic roles of NOT1 paralogues in the timing of gene expression inPlasmodium falciparum

Contact Info

Product

Resources

About