PXD025153

PXD025153 is an original dataset announced via ProteomeXchange.

Title	Trypanosome ZFP3 arginine residues are subject to modification by multiple methyltransferases and essential for transcriptome regulation
Description	The overall goal of this study was to identify methylated arginine residues on the Trypanosoma brucei RNA binding protein, ZFP3, and determine their functions in transcriptome regulation. We expressed Ty-tagged ZFP3 in procyclic form T. brucei, immunoprecipitated triplicate samples with anti-Ty antibodies, and subjected these samples to mass spectrometry to identify posttranslational modifications. We identified a highly methylated RGG domain, abundant R methylation at R109 in an unexpected context, and abundant tyrosine phosphorylation at Y4. To identify which protein arginine methyltransferases catalyzed these R methylation events, we performed in vitro methylation assays with TbPRMT1, TbPRMT6, and TbPRMT7 along with wild type and mutant ZFP3 substrates. These experiments showed that TbPRMT1 and TbPRMT7 methylate the RGG domain, while TbPRMT6 modifies R109. To ask how R methylations within affect ZFP3 transcriptome regulation, we overexpressed WT-ZFP3-Ty, R68,71K-ZFP3-Ty (hypomethylated) or R68,71F-ZFP3-Ty (methylmimic) in procyclic T. brucei. Overerexpression of WT-ZFP3-Ty lead to an increased expression of 749 tranascripts and decreased expression of 169 transcripts (1.5-fold change; padj<0.05). Overexpression of hypomethylated or methylmimic ZFP3 nearly abolished the capacity of ZFP3 to regulate three transcriptome, leading to changes in the abundances of less than 10 transcripts in either cell line. From these data, we conclude that arginine residues in the ZFP3 RGG domain are critical for its gene regulatory function.
HostingRepository	PRIDE
AnnounceDate	2021-05-26
AnnouncementXML	Submission_2021-05-25_22:06:15.444.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shichen Shen
SpeciesList	scientific name: Trypanosoma brucei; NCBI TaxID: 5691;
ModificationList	methylated residue; dimethylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-01 08:19:17	ID requested
1	2021-05-25 06:40:12	announced
⏵ 2	2021-05-25 22:06:15	announced	2021-05-26: Updated project metadata.

10.1016/J.CHEMBIOL.2021.03.012;

submitter keyword: ZFP3, arginine methylation,Trypanosoma brucei, methyltransferases

Laurie K. Read
contact affiliation	Department of Microbiology and Immunology, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
contact email	lread@buffalo.edu
lab head
Shichen Shen
contact affiliation	University at Buffalo
contact email	shichens@buffalo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025153
     1. Label: PRIDE project
     2. Name: Trypanosome ZFP3 arginine residues are subject to modification by multiple methyltransferases and essential for transcriptome regulation