The Plasmodium falciparum CCCH zinc finger protein MD3 regulates male gametocytogenesis through its interaction with RNA-binding proteins
© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd..
The transmission of malaria parasites to mosquitoes is dependent on the formation of gametocytes. Once fully matured, gametocytes are able to transform into gametes in the mosquito's midgut, a process accompanied with their egress from the enveloping erythrocyte. Gametocyte maturation and gametogenesis require a well-coordinated gene expression program that involves a wide spectrum of regulatory proteins, ranging from histone modifiers to transcription factors to RNA-binding proteins. Here, we investigated the role of the CCCH zinc finger protein MD3 in Plasmodium falciparum gametocytogenesis. MD3 was originally identified as an epigenetically regulated protein of immature gametocytes and recently shown to be involved in male development in a barcode-based screen in P. berghei. We report that MD3 is mainly present in the cytoplasm of immature male P. falciparum gametocytes. Parasites deficient of MD3 are impaired in gametocyte maturation and male gametocytogenesis. BioID analysis in combination with co-immunoprecipitation assays unveiled an interaction network of MD3 with RNA-binding proteins like PABP1 and ALBA3, with translational initiators, regulators and repressors like elF4G, PUF1, NOT1 and CITH, and with further regulators of gametocytogenesis, including ZNF4, MD1 and GD1. We conclude that MD3 is part of a regulator complex crucial for post-transcriptional fine-tuning of male gametocytogenesis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
Molecular microbiology - 121(2024), 3 vom: 15. März, Seite 543-564 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Farrukh, Afia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/mmi.15215 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366392298 |
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| 520 | |a © 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd. | ||
| 520 | |a The transmission of malaria parasites to mosquitoes is dependent on the formation of gametocytes. Once fully matured, gametocytes are able to transform into gametes in the mosquito's midgut, a process accompanied with their egress from the enveloping erythrocyte. Gametocyte maturation and gametogenesis require a well-coordinated gene expression program that involves a wide spectrum of regulatory proteins, ranging from histone modifiers to transcription factors to RNA-binding proteins. Here, we investigated the role of the CCCH zinc finger protein MD3 in Plasmodium falciparum gametocytogenesis. MD3 was originally identified as an epigenetically regulated protein of immature gametocytes and recently shown to be involved in male development in a barcode-based screen in P. berghei. We report that MD3 is mainly present in the cytoplasm of immature male P. falciparum gametocytes. Parasites deficient of MD3 are impaired in gametocyte maturation and male gametocytogenesis. BioID analysis in combination with co-immunoprecipitation assays unveiled an interaction network of MD3 with RNA-binding proteins like PABP1 and ALBA3, with translational initiators, regulators and repressors like elF4G, PUF1, NOT1 and CITH, and with further regulators of gametocytogenesis, including ZNF4, MD1 and GD1. We conclude that MD3 is part of a regulator complex crucial for post-transcriptional fine-tuning of male gametocytogenesis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Plasmodium falciparum | |
| 650 | 4 | |a CCCH zinc finger protein | |
| 650 | 4 | |a RNA-binding protein | |
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| 700 | 1 | |a Musabyimana, Jean Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Distler, Ute |e verfasserin |4 aut | |
| 700 | 1 | |a Mahlich, Vanessa Jil |e verfasserin |4 aut | |
| 700 | 1 | |a Mueller, Julius |e verfasserin |4 aut | |
| 700 | 1 | |a Bick, Fabian |e verfasserin |4 aut | |
| 700 | 1 | |a Tenzer, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Pradel, Gabriele |e verfasserin |4 aut | |
| 700 | 1 | |a Ngwa, Che Julius |e verfasserin |4 aut | |
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