PXD033957-1

PXD033957 is an original dataset announced via ProteomeXchange.

Title	The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity
Description	Artemisinin resistance in Plasmodium falciparum, clinically presented as prolonged parasite clearance half-life, has been associated with a mutation in the NLI-interacting factor-like phosphatase PfNIF4, in addition to the mutations in the Kelch13 protein as the major determinant. We found that PfNIF4 predominant expression at the schizont stage and localized in the nuclei of the parasite. To elucidate the functions of PfNIF4 in P. falciparum, we performed PfNIF4 knockdown (KD) using the inducible ribozyme system. PfNIF4 KD attenuated merozoite invasion and affected gametocytogenesis. PfNIF4 KD parasites also showed significantly increased in vitro susceptibility to artemisinins. Transcriptomic analysis revealed that PfNIF4 KD led to significant changes in the expression of approximately 10-25% of parasite genes during the IDC. At the schizont stage, down-regulated genes were significantly enriched in the invasion-related terms, while at the trophozoite and schizont stages, pathways associated with artemisinin resistance (e.g., mitochondrial function, membrane, and Kelch13 interactome) were also down-regulated. Consistent with PfNIF4 being a protein phosphatase, PfNIF4 KD resulted in an overall up-regulation of the phosphoproteome of infected erythrocytes. Specifically, we observed increased phosphorylation of Ser2/5 of the tandem repeats in the Rpb1 C-terminal domain (CTD) of RNA polymerase II (RNAPII) upon PfNIF4 KD. Furthermore, using the TurboID-based proteomic approach, we identified that PfNIF4 interacted with the RNA polymerase II (RNAPII) components, AP2-domain transcription factors, and chromatin-modifiers and binders. These findings suggest that PfNIF4 may act as the RNAPII CTD phosphatase, regulating the expression of general and parasite-specific cellular pathways during the blood-stage development.
HostingRepository	PRIDE
AnnounceDate	2022-07-23
AnnouncementXML	Submission_2022-07-23_05:18:39.316.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaotong Zhu
SpeciesList	scientific name: Plasmodium falciparum 3D7; NCBI TaxID: 36329;
ModificationList	phosphorylated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-18 04:28:49	ID requested
⏵ 1	2022-07-23 05:18:39	announced

Dataset with its publication pending

submitter keyword: Malaria

protein phosphatase

invasion

RNA polymerase II

asexual development

Xiaotong Zhu
contact affiliation	Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, China
contact email	xtzhu@cmu.edu.cn
lab head
Xiaotong Zhu
contact affiliation	Department of Immunology, College of Basic Medical Science, China Medical University
contact email	xtzhu@cmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD033957
     1. Label: PRIDE project
     2. Name: The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity