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Protein–RNA interactions important for Plasmodium transmission


Authors: Kelly T. Rios aff001;  Scott E. Lindner aff001
Authors place of work: Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, United States of America aff001
Published in the journal: Protein–RNA interactions important for Plasmodium transmission. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008095
Category: Pearls
doi: https://doi.org/10.1371/journal.ppat.1008095

Translational repression is a common regulatory mechanism used by both transmission stages

Gametocytes and sporozoites must both overcome similar obstacles. After fully maturing, they must lie in wait and be prepared for a fleeting moment when a mosquito takes a blood meal and thus move them between host and vector. After successfully transmitting, they find themselves in a hostile environment that they must exit as quickly as possible or face being digested in the mosquito midgut (gametocytes) or being targeted by antibodies and phagocytes (sporozoites). Because of this, the transmission stages rely heavily on post-transcriptional gene regulation [1], and though this is an energetically costly approach [2], it allows for the required rapid translational responses to environmental changes. Similarly, it is clear that translational repression is also used in a related Apicomplexa species, Toxoplasma gondii, for its specialized needs by using orthologous proteins [3, 4]. Together, this underscores the importance of preparedness.

Aside from the transmission stages, it remains controversial whether translational repression is also used in Plasmodium asexual stages [5, 6], with earlier studies reporting a discrepancy between mRNA and protein abundance in the asexual blood stages [7, 8], as well as differences in ribosome occupancy compared to peak transcript abundance [9]. However, a more recent report shows that transcription and translation are tightly coupled [10]. Despite this, translational control of var2csa has been well documented, showing that expression of an upstream open reading frame (uORF) and the action of the P. falciparum translation enhancing factor (PTEF) contribute to the translational regulation of var2csa [1114]. More work is certainly warranted to resolve the roles of these control mechanisms in this stage of the parasite’s life cycle.

Plasmodium parasites, like other eukaryotes, use two tiers of regulation to control the translation of mRNAs in transmission stages: specific translational repression of targeted mRNAs and global translational repression of most mRNAs (regulation in Plasmodium depicted in Fig 1, eukaryotic regulation reviewed in [15]). In sporozoites, global translational repression is enacted by a mechanism common to many eukaryotes that involves the regulation of the phosphorylation status of a specific serine residue (S59) on eukaryotic Initiation Factor 2α (eIF2α) by eIF2α kinase (eIK2/Up-regulated in Infectious Sporozoites 1 [UIS1]) to maintain parasite latency [3, 16, 17] and an eIF2α phosphatase (UIS2) to relieve repression following transmission. In contrast, specific translational repression relies upon interactions of RNA-binding proteins with specific mRNAs. In accordance with this possibly elevated role of post-transcriptional regulation, Plasmodium parasites have an unusually high proportion of RNA-binding proteins (approximately 10% of the annotated proteome) compared to other eukaryotes [18, 19]. In this scenario, specific transcripts are proactively generated in female gametocytes or sporozoites, which are then bound by RNA-binding proteins and trafficked to cytosolic granules to gain greater stability and to prevent/reduce their translation by the ribosome. While initial evidence for translational repression was seen in targeted studies of individual mRNAs such as p25 and p28 [20, 21] and of the DOZI RNA helicase (Development of Zygote Inhibited; an ortholog of DDX6, Dhh1) in gametocytes [22], evidence for the widespread use of translational repression in both transmission stages is now available from comparative transcriptomic and proteomic studies in gametocytes [23] and sporozoites [2426]. Moreover, our recent study has shown that sporozoites use two orthogonal translational repression programs during their maturation: one that represses mRNAs that encode for host cell traversal and infection functions that is relieved in salivary gland sporozoites and another that represses mRNAs used in early liver stage that is relieved upon transmission [24]. Thus, the use of both global and specific translational repression enables parasite preparedness and is crucial for effective parasite transmission.

Fig. 1. Overview of specific and global translational regulation in Plasmodium transmission stages.
Overview of specific and global translational regulation in <i>Plasmodium</i> transmission stages.
Specific transcripts are translationally repressed in female gametocytes (left) or salivary gland sporozoites (right) by stage-specific translational regulators. Translational repression of these transcripts is relieved following transmission, and the resulting proteins are essential for proper development and infection of the new host or vector. Global translational repression in sporozoites is controlled by the phosphorylation status of eIF2α by the kinase UIS1/eIK2, which is dominant in sporozoites, and the phosphatase UIS2, which is translationally repressed until the liver stage when it becomes active. eIF2α, eukaryotic Initiation Factor 2α; UIS, Up-regulated in Infectious Sporozoites.

What RNA–protein interactions are important in sporozoites for vector-to-host transmission?

Studies of specific translational repression in sporozoites have focused only on a handful of RNA-binding proteins, in part due to the technical difficulties of working with this parasite stage. Pumilio/FBF 2 (PUF2) and sporozoite asparagine-rich protein (SAP1)/sporozoite and liver stage asparagine-rich protein (SLARP) have been identified as RNA-binding proteins essential for sporozoite transmission and proper development in host hepatocytes, respectively. These proteins each localize to distinct granular complexes in the cytoplasm of salivary gland sporozoites [27, 28], and both contribute to the stabilization of transcripts important for liver stage development, including some of the UIS genes. SAP1/SLARP is essential for sporozoite infectivity and liver infection in P. yoelii and P. berghei, as parasites lacking this gene arrest early in liver stage development [29, 30]. Comparative transcriptomic analysis between pysap1and wild-type salivary gland sporozoites demonstrated that PySAP1 contributes to the preservation of UIS transcripts important for liver stage development [28]. In fact, the deletion of sap1 in either P. yoelii or P. berghei results in greatly reduced UIS transcript abundance, including uis3 and uis4, and pysap1 parasites do not express UIS3 or UIS4 proteins in liver stage parasites when they are required [2932]. In contrast, PUF2 is responsible for maintaining the latency and infectivity of salivary gland sporozoites, as P. yoelii and P. berghei puf2 sporozoites lose infectivity and, remarkably, begin to prematurely dedifferentiate into liver stage-like forms during prolonged residence in the salivary glands [27, 33, 34]. Comparative transcriptomic analysis between pypuf2 and wild-type salivary gland sporozoites showed that there is large-scale dysregulation in mRNA abundances in the absence of PUF2 that precedes the loss of infectivity and that the parasites can overcome this defect if they transmit in time [27]. PUF-family proteins are known to regulate transcripts by binding to an adenylate-uridylate (AU)-rich PUF-binding element (PBE) that is usually found in the untranslated regions (UTRs) of mRNAs. However, the best studied PUF2-regulated mRNA in sporozoites, uis4, appears to be bound and translationally repressed when PUF2 associates with one or more PBEs found in its coding region [35, 36]. Following hepatocyte invasion, the PUF2 granules dissolve [27], and uis4 mRNA is derepressed [36]. Finally, global and specific translational repression are intertwined in sporozoites, as the mRNA of the UIS2 phosphatase responsible for relieving global translational repression via eIF2α dephosphorylation is regulated by PUF2, thus allowing a stepwise and controlled program of development [17, 37]. While the transcripts for uis1 and uis2 are among the most up-regulated and abundant transcripts in salivary gland sporozoites, specific translational repression dictates which activity predominates in sporozoites (UIS1) and liver stages (UIS2). Analogous to the phenotype of puf2 sporozoites, the deletion of uis1 results in parasites that prematurely transform into exoerythrocytic-like forms and lose their infectivity [17].

What RNA–protein interactions are important in gametocytes for host-to-vector transmission?

The infection of a mosquito by Plasmodium parasites requires the activation of gametocytes into gametes upon arrival in the midgut of the mosquito and is triggered by extracellular cues, like changes in temperature, the presence of xanthurenic acid, and likely other unappreciated factors [38]. These extracellular changes trigger a signaling cascade propagated by parasite-specific calcium-dependent protein kinases (CDPKs) [39], including CDPK1, which relieves translational repression of transcripts after fertilization occurs in the mosquito midgut [40]. In addition, RNA–protein interactions and post-transcriptional gene regulation are also critical to the infection of mosquitoes and have been easier to study in gametocytes because they are easier to produce/purify en masse and to phenotype in comparison to sporozoites. Two of the major RNA-binding proteins that confer translational repression in female gametocytes are the DEAD-box RNA helicase DOZI (an orthologue of human DDX6 and yeast Dhh1) and the Sm-like factor CITH (homolog of CAR-I and Trailer Hitch; an orthologue of LSM14A) [22, 41]. These two proteins are required for the stabilization of hundreds of transcripts in female gametocytes and are essential for parasite development after fertilization in the mosquito midgut [22, 41]. DOZI and CITH interact with many of the important transcripts that they stabilize, including some of the most highly expressed transcripts in gametocytes, like ookinete surface proteins p25, and p28, and a mosquito-stage specific transcription factor ap2-o [42]. This proper regulation of protein expression of P25, P28, and AP2-O proteins is required for oocyst development in the mosquito [21, 43, 44]. Additionally, DOZI and CITH also translationally repress limp, which is translated in the ookinete from maternal mRNA and is a key regulator for adhesion during gliding motility [45]. Finally, coimmunoprecipitation experiments identified additional RNA-binding factors that interact with DOZI and CITH, including translation initiation factor eIF4E, poly(A)-binding protein 1, Bruno/HoBo, Musashi, 7-helix-1, and ALBA-family proteins 1 through 4 [41, 46, 47]. In particular, PyALBA4 plays a role in transcript preservation in gametocytes, including mRNAs from LCCL-domain–containing genes that are important for early mosquito-stage infection, like lap4, lap5, and lap6 [47].

Along with their roles in sporozoites, PUF-family proteins also play important roles in female gametocytes. PUF1 was shown to be important for the differentiation and maintenance of P. falciparum gametocytes [48], whereas PUF2 is important for the regulation of gametocytogenesis in a sex-dependent manner, as pbpuf2 and pfpuf2 (but not pypuf2) parasites make more gametocytes than wild type and have a disrupted male:female gametocyte ratio [27, 33, 49]. And while PUF2 traffics to a complex that is distinct from the DOZI/CITH complex, both complexes have overlapping mRNA targets, like p25 and p28 [50]. Moreover, in vitro rabbit reticulocyte translation assays demonstrated that PfPUF2 is both the necessary and sufficient Plasmodium trans-factor to translationally repress p25 and p28 or chimeric mRNAs containing specific PBEs from their UTRs [50].

Final takeaways and outstanding questions

Translational repression is energetically costly, so there is likely an important reason the parasites use it instead of simply regulating transcription: it allows both readiness and rapid responsiveness to stimuli. However, the use of translational repression allows for an intermediate level of investment: mRNA is made, but the price to produce protein has not yet been paid. Of course, an even more rapid response to stimuli could be achieved by producing the proteins and retaining them in an inactive state. However, this is much more energetically expensive, and the consequences of prematurely expressing (or activating) proteins are dire for transmission stages, as this has been shown to render them noninfectious for both Plasmodium gametocytes and sporozoites. Therefore, it is perhaps not surprising that translational repression is subject to multiple tiers of control by both global and specific programs, as well as a diverse and expanded set of RNA-binding proteins that target similar transcripts [19].

While much is now known about how translational repression is used by Plasmodium transmission-stage parasites, many outstanding questions remain.

  • What initiates specific translational repression of mRNAs? This regulation could be imposed from the birth of a transcript in the nucleus by RNA-binding protein association and imprinting, at its receipt by a granule positioned over the exit site of the nuclear pore complex, or even later in the cytosol if a stimulus-specific event switches the program on.

  • How are the mRNA–protein granules organized? Substantial work has been done to investigate similar cytosolic granules in yeast, which now invokes a nonuniform, liquid–liquid phase separation model that allows for the docking and locking of mRNAs into these granules [51]. Does Plasmodium use a similar strategy for one or both of its transmission stages?

  • What are the external stimuli that initiate the dissolution of cytosolic granules post transmission, and what is the mechanism of dissolution? The most obvious common stimulus is that both gametocytes and sporozoites undergo substantial temperature swings between ambient temperatures and 37°C. However, the directionality of this change is opposite for the two stages, and thus the effect of temperature change upon granule stability would be as well. Could temperature changes instead affect enzymes that can install or remove post-translational modifications (e.g., phosphate groups) that stabilize or destabilize protein–mRNA interactions?

  • Finally, could there be a role for translational repression in male gametocytes as well? The deletion of genes encoding several RNA-binding proteins also results in male-specific phenotypes, such as an increase, decrease, or ablation of exflagellation. It is feasible that any life cycle stage that requires a rapid response to environmental stimuli could rely upon this strategy.

It is clear that Plasmodium has evolved to rely heavily upon post-transcriptional regulation and that many of the same effector proteins are used and repurposed for functionally similar purposes across the life cycle. Future efforts that address the above questions will ultimately help to pinpoint and exploit key weaknesses and could be used to help control parasite transmission.


Zdroje

1. Cui L, Lindner S, Miao J. Translational regulation during stage transitions in malaria parasites. Ann N Y Acad Sci. 2015;1342:1–9. Epub 2014/11/13. doi: 10.1111/nyas.12573 25387887; PubMed Central PMCID: PMC4405408.

2. Hausser J, Mayo A, Keren L, Alon U. Central dogma rates and the trade-off between precision and economy in gene expression. Nat Commun. 2019;10(1):68. Epub 2019/01/10. doi: 10.1038/s41467-018-07391-8 30622246; PubMed Central PMCID: PMC6325141.

3. Holmes MJ, Augusto LDS, Zhang M, Wek RC, Sullivan WJ Jr. Translational Control in the Latency of Apicomplexan Parasites. Trends Parasitol. 2017;33(12):947–60. Epub 2017/09/25. doi: 10.1016/j.pt.2017.08.006 28942109; PubMed Central PMCID: PMC5705472.

4. Cherry AA, Ananvoranich S. Characterization of a homolog of DEAD-box RNA helicases in Toxoplasma gondii as a marker of cytoplasmic mRNP stress granules. Gene. 2014;543(1):34–44. Epub 2014/04/09. doi: 10.1016/j.gene.2014.04.011 24709106.

5. Vembar SS, Droll D, Scherf A. Translational regulation in blood stages of the malaria parasite Plasmodium spp.: systems-wide studies pave the way. Wiley Interdiscip Rev RNA. 2016;7(6):772–92. Epub 2016/05/28. doi: 10.1002/wrna.1365 27230797; PubMed Central PMCID: PMC5111744.

6. Vembar SS, Macpherson CR, Sismeiro O, Coppee JY, Scherf A. The PfAlba1 RNA-binding protein is an important regulator of translational timing in Plasmodium falciparum blood stages. Genome Biol. 2015;16:212. Epub 2015/09/30. doi: 10.1186/s13059-015-0771-5 26415947; PubMed Central PMCID: PMC4587749.

7. Foth BJ, Zhang N, Mok S, Preiser PR, Bozdech Z. Quantitative protein expression profiling reveals extensive post-transcriptional regulation and post-translational modifications in schizont-stage malaria parasites. Genome Biol. 2008;9(12):R177. Epub 2008/12/19. doi: 10.1186/gb-2008-9-12-r177 19091060; PubMed Central PMCID: PMC2646281.

8. Le Roch KG, Johnson JR, Florens L, Zhou Y, Santrosyan A, Grainger M, et al. Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle. Genome Res. 2004;14(11):2308–18. Epub 2004/11/03. doi: 10.1101/gr.2523904 15520293; PubMed Central PMCID: PMC525690.

9. Bunnik EM, Chung DW, Hamilton M, Ponts N, Saraf A, Prudhomme J, et al. Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum. Genome Biol. 2013;14(11):R128. Epub 2013/11/26. doi: 10.1186/gb-2013-14-11-r128 24267660; PubMed Central PMCID: PMC4053746.

10. Caro F, Ahyong V, Betegon M, DeRisi JL. Genome-wide regulatory dynamics of translation in the Plasmodium falciparum asexual blood stages. Elife. 2014;3. Epub 2014/12/11. doi: 10.7554/eLife.04106 25493618; PubMed Central PMCID: PMC4371882.

11. Chan S, Frasch A, Mandava CS, Ch'ng JH, Quintana MDP, Vesterlund M, et al. Regulation of PfEMP1-VAR2CSA translation by a Plasmodium translation-enhancing factor. Nat Microbiol. 2017;2:17068. Epub 2017/05/10. doi: 10.1038/nmicrobiol.2017.68 28481333.

12. Bancells C, Deitsch KW. A molecular switch in the efficiency of translation reinitiation controls expression of var2csa, a gene implicated in pregnancy-associated malaria. Mol Microbiol. 2013;90(3):472–88. Epub 2013/08/29. doi: 10.1111/mmi.12379 23980802; PubMed Central PMCID: PMC3938558.

13. Amulic B, Salanti A, Lavstsen T, Nielsen MA, Deitsch KW. An upstream open reading frame controls translation of var2csa, a gene implicated in placental malaria. PLoS Pathog. 2009;5(1):e1000256. Epub 2009/01/03. doi: 10.1371/journal.ppat.1000256 19119419; PubMed Central PMCID: PMC2603286.

14. Mok BW, Ribacke U, Rasti N, Kironde F, Chen Q, Nilsson P, et al. Default Pathway of var2csa switching and translational repression in Plasmodium falciparum. PLoS ONE. 2008;3(4):e1982. Epub 2008/04/24. doi: 10.1371/journal.pone.0001982 18431472; PubMed Central PMCID: PMC2292259.

15. Sonenberg N, Hinnebusch AG. Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell. 2009;136(4):731–45. Epub 2009/02/26. doi: 10.1016/j.cell.2009.01.042 19239892; PubMed Central PMCID: PMC3610329.

16. Turque O, Tsao T, Li T, Zhang M. Translational Repression in Malaria Sporozoites. Microb Cell. 2016;3(5):227–9. Epub 2017/03/31. doi: 10.15698/mic2016.05.502 28357358; PubMed Central PMCID: PMC5349151.

17. Zhang M, Fennell C, Ranford-Cartwright L, Sakthivel R, Gueirard P, Meister S, et al. The Plasmodium eukaryotic initiation factor-2alpha kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. J Exp Med. 2010;207(7):1465–74. Epub 2010/06/30. doi: 10.1084/jem.20091975 20584882; PubMed Central PMCID: PMC2901070.

18. Bunnik EM, Batugedara G, Saraf A, Prudhomme J, Florens L, Le Roch KG. The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum. Genome Biol. 2016;17(1):147. Epub 2016/07/07. doi: 10.1186/s13059-016-1014-0 27381095; PubMed Central PMCID: PMC4933991.

19. Reddy BP, Shrestha S, Hart KJ, Liang X, Kemirembe K, Cui L, et al. A bioinformatic survey of RNA-binding proteins in Plasmodium. BMC Genomics. 2015;16:890. Epub 2015/11/04. doi: 10.1186/s12864-015-2092-1 26525978; PubMed Central PMCID: PMC4630921.

20. del Carmen Rodriguez M, Gerold P, Dessens J, Kurtenbach K, Schwartz RT, Sinden RE, et al. Characterisation and expression of pbs25, a sexual and sporogonic stage specific protein of Plasmodium berghei. Mol Biochem Parasitol. 2000;110(1):147–59. Epub 2000/09/16. doi: 10.1016/s0166-6851(00)00265-6 10989152.

21. Paton MG, Barker GC, Matsuoka H, Ramesar J, Janse CJ, Waters AP, et al. Structure and expression of a post-transcriptionally regulated malaria gene encoding a surface protein from the sexual stages of Plasmodium berghei. Mol Biochem Parasitol. 1993;59(2):263–75. Epub 1993/06/01. doi: 10.1016/0166-6851(93)90224-l 8341324.

22. Mair GR, Braks JA, Garver LS, Wiegant JC, Hall N, Dirks RW, et al. Regulation of sexual development of Plasmodium by translational repression. Science. 2006;313(5787):667–9. Epub 2006/08/05. doi: 10.1126/science.1125129 16888139; PubMed Central PMCID: PMC1609190.

23. Lasonder E, Rijpma SR, van Schaijk BC, Hoeijmakers WA, Kensche PR, Gresnigt MS, et al. Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes: molecular insight into sex-specific processes and translational repression. Nucleic Acids Res. 2016;44(13):6087–101. Epub 2016/06/15. doi: 10.1093/nar/gkw536 27298255; PubMed Central PMCID: PMC5291273.

24. Lindner SE, Swearingen KE, Shears MJ, Walker MP, Vrana EN, Hart KJ, et al. Transcriptomics and proteomics reveal two waves of translational repression during maturation of malaria parasite sporozoites. Nat Commun. 2019;10(1):4964. doi: 10.1038/s41467-019-12936-6 31673027

25. Swearingen KE, Lindner SE, Flannery EL, Vaughan AM, Morrison RD, Patrapuvich R, et al. Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium vivax salivary gland sporozoites. PLoS Negl Trop Dis. 2017;11(7):e0005791. Epub 2017/08/02. doi: 10.1371/journal.pntd.0005791 28759593; PubMed Central PMCID: PMC5552340.

26. Vivax Sporozoite C. Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria. Int J Parasitol. 2019;49(7):501–13. Epub 2019/05/10. doi: 10.1016/j.ijpara.2019.02.007 31071319.

27. Lindner SE, Mikolajczak SA, Vaughan AM, Moon W, Joyce BR, Sullivan WJ Jr., et al. Perturbations of Plasmodium Puf2 expression and RNA-seq of Puf2-deficient sporozoites reveal a critical role in maintaining RNA homeostasis and parasite transmissibility. Cell Microbiol. 2013;15(7):1266–83. Epub 2013/01/30. doi: 10.1111/cmi.12116 23356439; PubMed Central PMCID: PMC3815636.

28. Aly AS, Lindner SE, MacKellar DC, Peng X, Kappe SH. SAP1 is a critical post-transcriptional regulator of infectivity in malaria parasite sporozoite stages. Mol Microbiol. 2011;79(4):929–39. Epub 2011/02/09. doi: 10.1111/j.1365-2958.2010.07497.x 21299648.

29. Silvie O, Goetz K, Matuschewski K. A sporozoite asparagine-rich protein controls initiation of Plasmodium liver stage development. PLoS Pathog. 2008;4(6):e1000086. Epub 2008/06/14. doi: 10.1371/journal.ppat.1000086 18551171; PubMed Central PMCID: PMC2398788.

30. Aly AS, Mikolajczak SA, Rivera HS, Camargo N, Jacobs-Lorena V, Labaied M, et al. Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection. Mol Microbiol. 2008;69(1):152–63. Epub 2008/05/10. doi: 10.1111/j.1365-2958.2008.06271.x 18466298; PubMed Central PMCID: PMC2615191.

31. Tarun AS, Dumpit RF, Camargo N, Labaied M, Liu P, Takagi A, et al. Protracted sterile protection with Plasmodium yoelii pre-erythrocytic genetically attenuated parasite malaria vaccines is independent of significant liver-stage persistence and is mediated by CD8+ T cells. J Infect Dis. 2007;196(4):608–16. Epub 2007/07/13. doi: 10.1086/519742 17624848.

32. Mueller AK, Labaied M, Kappe SH, Matuschewski K. Genetically modified Plasmodium parasites as a protective experimental malaria vaccine. Nature. 2005;433(7022):164–7. Epub 2004/12/08. doi: 10.1038/nature03188 15580261.

33. Muller K, Matuschewski K, Silvie O. The Puf-family RNA-binding protein Puf2 controls sporozoite conversion to liver stages in the malaria parasite. PLoS ONE. 2011;6(5):e19860. Epub 2011/06/16. doi: 10.1371/journal.pone.0019860 21673790; PubMed Central PMCID: PMC3097211.

34. Yanagi K, Ohyama K, Yamakawa T, Watanabe H, Hirakawa S, Ohkuma S. [Separation of Thomsen-Friedenreich (T) antigen and N antigen precursor glycoproteins from perchloric acid-soluble fraction of cyst fluid of human ovarian clear cell carcinoma and their some chemical and serological properties]. Yakugaku Zasshi. 1990;110(4):273–9. Epub 1990/04/01. doi: 10.1248/yakushi1947.110.4_273 2165527.

35. Silva PA, Guerreiro A, Santos JM, Braks JA, Janse CJ, Mair GR. Translational Control of UIS4 Protein of the Host-Parasite Interface Is Mediated by the RNA Binding Protein Puf2 in Plasmodium berghei Sporozoites. PLoS ONE. 2016;11(1):e0147940. Epub 2016/01/26. doi: 10.1371/journal.pone.0147940 26808677; PubMed Central PMCID: PMC4726560.

36. Silvie O, Briquet S, Muller K, Manzoni G, Matuschewski K. Post-transcriptional silencing of UIS4 in Plasmodium berghei sporozoites is important for host switch. Mol Microbiol. 2014;91(6):1200–13. Epub 2014/01/23. doi: 10.1111/mmi.12528 24446886.

37. Zhang M, Mishra S, Sakthivel R, Fontoura BM, Nussenzweig V. UIS2: A Unique Phosphatase Required for the Development of Plasmodium Liver Stages. PLoS Pathog. 2016;12(1):e1005370. Epub 2016/01/07. doi: 10.1371/journal.ppat.1005370 26735921; PubMed Central PMCID: PMC4712141.

38. Billker O, Lindo V, Panico M, Etienne AE, Paxton T, Dell A, et al. Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature. 1998;392(6673):289–92. Epub 1998/04/01. doi: 10.1038/32667 9521324.

39. Brochet M, Billker O. Calcium signalling in malaria parasites. Mol Microbiol. 2016;100(3):397–408. Epub 2016/01/11. doi: 10.1111/mmi.13324 26748879.

40. Sebastian S, Brochet M, Collins MO, Schwach F, Jones ML, Goulding D, et al. A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs. Cell Host Microbe. 2012;12(1):9–19. Epub 2012/07/24. doi: 10.1016/j.chom.2012.05.014 22817984; PubMed Central PMCID: PMC3414820.

41. Mair GR, Lasonder E, Garver LS, Franke-Fayard BM, Carret CK, Wiegant JC, et al. Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 2010;6(2):e1000767. Epub 2010/02/20. doi: 10.1371/journal.ppat.1000767 20169188; PubMed Central PMCID: PMC2820534.

42. Guerreiro A, Deligianni E, Santos JM, Silva PA, Louis C, Pain A, et al. Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte. Genome Biol. 2014;15(11):493. Epub 2014/11/25. doi: 10.1186/s13059-014-0493-0 25418785; PubMed Central PMCID: PMC4234863.

43. Yuda M, Iwanaga S, Shigenobu S, Mair GR, Janse CJ, Waters AP, et al. Identification of a transcription factor in the mosquito-invasive stage of malaria parasites. Mol Microbiol. 2009;71(6):1402–14. Epub 2009/02/18. doi: 10.1111/j.1365-2958.2009.06609.x 19220746.

44. Tomas AM, Margos G, Dimopoulos G, van Lin LH, de Koning-Ward TF, Sinha R, et al. P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO J. 2001;20(15):3975–83. Epub 2001/08/03. doi: 10.1093/emboj/20.15.3975 11483501; PubMed Central PMCID: PMC149139.

45. Santos JM, Egarter S, Zuzarte-Luis V, Kumar H, Moreau CA, Kehrer J, et al. Malaria parasite LIMP protein regulates sporozoite gliding motility and infectivity in mosquito and mammalian hosts. Elife. 2017;6. Epub 2017/05/20. doi: 10.7554/eLife.24109 28525314; PubMed Central PMCID: PMC5438254.

46. Bennink S, von Bohl A, Ngwa CJ, Henschel L, Kuehn A, Pilch N, et al. A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum. PLoS Pathog. 2018;14(8):e1007249. Epub 2018/08/23. doi: 10.1371/journal.ppat.1007249 30133543; PubMed Central PMCID: PMC6122839.

47. Munoz EE, Hart KJ, Walker MP, Kennedy MF, Shipley MM, Lindner SE. ALBA4 modulates its stage-specific interactions and specific mRNA fates during Plasmodium yoelii growth and transmission. Mol Microbiol. 2017;106(2):266–84. Epub 2017/08/09. doi: 10.1111/mmi.13762 28787542; PubMed Central PMCID: PMC5688949.

48. Shrestha S, Li X, Ning G, Miao J, Cui L. The RNA-binding protein Puf1 functions in the maintenance of gametocytes in Plasmodium falciparum. J Cell Sci. 2016;129(16):3144–52. Epub 2016/07/08. doi: 10.1242/jcs.186908 27383769; PubMed Central PMCID: PMC5004898.

49. Miao J, Li J, Fan Q, Li X, Li X, Cui L. The Puf-family RNA-binding protein PfPuf2 regulates sexual development and sex differentiation in the malaria parasite Plasmodium falciparum. J Cell Sci. 2010;123(Pt 7):1039–49. Epub 2010/03/04. doi: 10.1242/jcs.059824 20197405; PubMed Central PMCID: PMC2844316.

50. Miao J, Fan Q, Parker D, Li X, Li J, Cui L. Puf mediates translation repression of transmission-blocking vaccine candidates in malaria parasites. PLoS Pathog. 2013;9(4):e1003268. Epub 2013/05/03. doi: 10.1371/journal.ppat.1003268 23637595; PubMed Central PMCID: PMC3630172.

51. Moon SL, Morisaki T, Khong A, Lyon K, Parker R, Stasevich TJ. Multicolour single-molecule tracking of mRNA interactions with RNP granules. Nat Cell Biol. 2019;21(2):162–8. Epub 2019/01/22. doi: 10.1038/s41556-018-0263-4 30664789; PubMed Central PMCID: PMC6375083.

Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř

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PLOS Pathogens


2019 Číslo 12
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