PXD066690-1

PXD066690 is an original dataset announced via ProteomeXchange.

Title	METTL1 Interacts with XPO5 to Modulate Pre-miRNA Export
Description	tRNA methylguanosine methyltransferase 1 (METTL1) is the prominent m7G writer protein in yeast and human cells. While several studies documented the transcriptome-wide distributions of METTL1-installed m7G, very little is known about the protein-protein interactions (PPI) involving METTL1. To fill in this knowledge gap, we adopted an engineered ascorbate peroxidase (APEX)-based proximity labeling, followed by LC-MS/MS analysis, to investigate the METTL1 interactome in HEK293T cells. We identified more than 70 unique proteins enriched in the proximity proteome of METTL1, and verified METTL1’s interaction with one of these proteins, exportin 5 (XPO5) through co-immunoprecipitation followed by immunoblot analysis. We also revealed that genetic ablation of METTL1 led to elevated distribution of XPO5 in the cytosol, thereby enhancing pre-miRNA export and miRNA maturation. Mechanistically, METTL1 promotes ERK-mediated phosphorylation of XPO5, which leads to its augmented nuclear retention. Ectopic expression of a constitutively active form of MEK, i.e., MEKDD, restored XPO5’s nuclear localization in METTL1-deficient cells, suggesting that METTL1 modulates miRNA processing through a mechanism independent of its catalytic activity. Together, we uncovered a novel role of METTL1 in modulating XPO5’s subcellular distribution and pre-miRNA export through its interaction with XPO5, and we also revealed a novel mechanism of miRNA maturation and expanded METTL1’s function beyond m7G methylation.
HostingRepository	PRIDE
AnnounceDate	2026-02-02
AnnouncementXML	Submission_2026-02-01_16:27:42.613.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhongwen Cao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	biotinylated residue; iodoacetic acid derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-28 20:15:28	ID requested
⏵ 1	2026-02-01 16:27:43	announced

Cao Z, Chen X, Sun Y, Wang Y, METTL1 interacts with XPO5 to modulate pre-miRNA export. Nucleic Acids Res, 54(3):(2026) [pubmed]

10.1093/nar/gkag037;

submitter keyword: affinity labeling, miRNA,LC-MSMS

Yinsheng Wang
contact affiliation	University of California, Riverside
contact email	yinsheng@ucr.edu
lab head
Zhongwen Cao
contact affiliation	University of California, Riverside
contact email	zcao037@ucr.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066690
     1. Label: PRIDE project
     2. Name: METTL1 Interacts with XPO5 to Modulate Pre-miRNA Export