Guzzi et al. 2021 (PRJNA680364)

General Details

Title Ribosome profiling of H9 PUS7KO
Organism
Number of Samples 4
Release Date 2020/11/23 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP293929
ENA SRP293929
GEO GSE162050
BioProject PRJNA680364

Publication

Title
Authors Guzzi N, Muthukumar S, Cieśla M, Todisco G, Ngoc PCT, Madej M, Munita R, Fazio S, Ekström S, Mortera-Blanco T, Jansson M, Nannya Y, Cazzola M, Ogawa S, Malcovati L, Hellström-Lindberg E, Dimitriou M, Bellodi C
Journal Nature cell biology
Publication Date 2022 Mar
Abstract Transfer RNA-derived fragments (tRFs) are emerging small noncoding RNAs that, although commonly altered in cancer, have poorly defined roles in tumorigenesis 1 . Here we show that pseudouridylation (Ψ) of a stem cell-enriched tRF subtype 2 , mini tRFs containing a 5' terminal oligoguanine (mTOG), selectively inhibits aberrant protein synthesis programmes, thereby promoting engraftment and differentiation of haematopoietic stem and progenitor cells (HSPCs) in patients with myelodysplastic syndrome (MDS). Building on evidence that mTOG-Ψ targets polyadenylate-binding protein cytoplasmic 1 (PABPC1), we employed isotope exchange proteomics to reveal critical interactions between mTOG and functional RNA-recognition motif (RRM) domains of PABPC1. Mechanistically, this hinders the recruitment of translational co-activator PABPC1-interacting protein 1 (PAIP1) 3 and strongly represses the translation of transcripts sharing pyrimidine-enriched sequences (PES) at the 5' untranslated region (UTR), including 5' terminal oligopyrimidine tracts (TOP) that encode protein machinery components and are frequently altered in cancer 4 . Significantly, mTOG dysregulation leads to aberrantly increased translation of 5' PES messenger RNA (mRNA) in malignant MDS-HSPCs and is clinically associated with leukaemic transformation and reduced patient survival. These findings define a critical role for tRFs and Ψ in difficult-to-treat subsets of MDS characterized by high risk of progression to acute myeloid leukaemia (AML). © 2022. The Author(s).
PMC PMC8924001
PMID 35292784
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR13120321 PRJNA680364 Homo sapiens H9 Ribo-Seq 0.0
SRR13120322 PRJNA680364 Homo sapiens H9 Ribo-Seq 0.0
SRR13120323 PRJNA680364 Homo sapiens H9 Ribo-Seq 0.0
SRR13120324 PRJNA680364 Homo sapiens H9 Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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