Document Type
Article
Publication Date
12-1-2025
Original Citation
Shamloo S,
Schloßhauer J,
Tiwari S,
Denise Fischer K,
Almolla O,
Ghebrechristos Y,
Kratzenberg L,
Bejoy A,
Aifantis I,
Boccalatte F,
Wang E,
Imig J.
RNA binding of GAPDH controls transcript stability and protein translation in acute myeloid leukemia. RNA Biol. 2025;22(1):1–23
Keywords
JGM, Humans, Leukemia, Myeloid, Acute, Glyceraldehyde-3-Phosphate Dehydrogenases, Protein Biosynthesis, RNA, Messenger, RNA-Binding Proteins, 5' Untranslated Regions, Cell Line, Tumor, RNA Stability, Protein Binding, Gene Expression Regulation, Leukemic, Cell Proliferation, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
JAX Source
RNA Biol. 2025;22(1):1–23
ISSN
1555-8584
PMID
41175344
DOI
https://doi.org/10.1080/15476286.2025.2580180
Grant
E.W. is supported by The Jackson Laboratory Cancer Center (JAXCC) New Investigator Award (P30CA034196), JAX start-up funds, JAX Cancer Center Fast Forward Award, American Society of Hematology (ASH) Scholar Award, Leukemia Research Foundation (LRF), Alex’s Lemonade Stand Foundation for Childhood Cancer and Start-Up grant from Associazione Italiana Ricerca sul Cancro (AIRC)[26533]
Abstract
Dysregulation of RNA binding proteins (RBPs) is a hallmark in cancerous cells. In acute myeloid leukaemia (AML) RBPs are key regulators of tumour proliferation. While classical RBPs have defined RNA binding domains, RNA recognition and function in AML by non-canonical RBPs (ncRBPs) remain unclear. Given the inherent complexity of targeting AML broadly, our goal was to uncover potential ncRBP candidates critical for AML survival using a CRISPR/Cas-based screening. We identified the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a pro-proliferative factor in AML cells. Based on cross-linking and immunoprecipitation (CLIP), we are defining the global targetome, detecting novel RNA targets mainly located within 5'UTRs, including GAPDH, RPL13a, and PKM. The knockdown of GAPDH unveiled genetic pathways related to ribosome biogenesis, translation initiation, and regulation. Moreover, we demonstrated a stabilizing effect through GAPDH binding to target transcripts including its own mRNA. The present findings provide new insights on the RNA functions and characteristics of GAPDH in AML.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.