Ribosome changes reprogram translation for chemosurvival in G0 leukemic cells
Year: 2022
Type: article
Abstract: Quiescent leukemic cells survive chemotherapy, with translation changes. Our data reveal that FXR1, a protein amplified in several aggressive cancers, is elevated in quiescent and chemo-treated leukemic cells and promotes chemosurvival. This suggests undiscovered roles for this RNA- and ribosome-associated protein in chemosurvival. We find that FXR1 depletion reduces translation, with altered rRNAs, snoRNAs, and ribosomal proteins (RPs). FXR1 regulates factors that promote transcription and processing of ribosomal genes and snoRNAs. Ribosome changes in FXR1-overexpressing cells, including RPLP0/uL10 levels, activate eIF2α kinases. Accordingly, phospho-eIF2α increases, enabling selective translation of survival and immune regulators in FXR1-overexpressing cells. Overriding these genes or phospho-eIF2α with inhibitors reduces chemosurvival. Thus, elevated FXR1 in quiescent or chemo-treated leukemic cells alters ribosomes that trigger stress signals to redirect translation for chemosurvival.
Source: Science Advances
Institutions: Harvard University, Massachusetts General Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: Standardized Molecular Analyses of Glioma EVs, Specialized post-transcriptional mechanisms of gene expression in quiescence, Imaging and Liquid Biopsy for Glioma Diagnosis and Treatment Monitoring, Liquid Biopsy for treatment stratification of IDH1.R132H and EGFRvIII mutant gliomas, Role of RNA methylation in chemoresistant cancer cells
OpenAlex ID: W4307475378