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PXD023122-1

PXD023122 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePseudouridine-modified tRNA fragments repress malignant protein synthesis and predict leukemic progression in myelodysplastic syndrome
DescriptionTransfer RNA (tRNA)-derived fragments (tRF) are emerging small noncoding (nc) RNAs that, while commonly altered in cancer, have poorly defined roles in tumorigenesis. Here we show that pseudouridylation (Ψ) of a stem-cell-enriched tRF subtype, mTOG, selectively inhibits malignant protein synthesis programs, thereby promoting engraftment and differentiation of myelodysplastic syndrome (MDS) hematopoietic stem and progenitor cells (HSPC). Building on evidence that mTOG-Ψ target the polyadenylate-binding protein cytoplasmic 1 (PABPC1), we employed HDX-MS to reveal critical interactions between mTOG and functional RNA-recognition motif (RRM) domains in PABPC1. Mechanistically, this hinders the recruitment of the translational co-activator PABPC1-interacting protein 1 (PAIP1) and strongly represses translation of transcripts sharing 5’UTR pyrimidine-enriched sequences (PES), including 5’ terminal oligopyrimidine tracts (TOP) that encode protein machinery components, and are frequently altered in cancer. Significantly, mTOG dysregulation leads to aberrantly increased 5’PES mRNA translation in malignant MDS-HSPC and is clinically associated with leukemic transformation and reduced patient survival. Taken together, these results define a critical role for tRF and Ψ in difficult-to-treat subsets of MDS characterized by high risk of progression to acute myeloid leukemia.
HostingRepositoryPRIDE
AnnounceDate2021-12-20
AnnouncementXMLSubmission_2021-12-20_04:22:29.102.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSimon Ekström
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-12-14 06:44:45ID requested
12021-12-20 04:22:29announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: RNA modifications
development
hematopoiesis
pseudouridine
stem cells
tRNA fragments
translation control. HDX MS
Contact List
Cristian Bellodi
contact affiliationDivision of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund, Sweden
contact emailcristian.bellodi@med.lu.se
lab head
Simon Ekström
contact affiliationBioMS - Swedish National Infrastructure for Biological Mass Spectrometry, Lund University, BMC D1330, 221 84 Lund, Sweden
contact emailsimon.ekstrom@med.lu.se
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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