Photo Credit: Nemes Laszlo
A recent study revealed elevated methyltransferase 1-WD repeat-containing protein 4 (METTL1-WDR4) levels in acute myeloid leukemia (AML), linking it to poor prognosis, and underscoring its crucial role in AML leukemogenesis, suggesting it as a potential therapeutic target.
The following is a summary of “METTL1 mediated tRNA m7G modification promotes leukemogenesis of AML via tRNA regulated translational control,” published in the January 2024 issue of Hematology by Zhao et al.
In this study, the investigators investigate the vital role of RNA modifications, particularly the maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4, in the context of oncogenic processes across various cancers. While the oncogenic roles of METTL1/WDR4 in multiple cancers have been established, their specific functions and molecular mechanisms in acute myeloid leukemia (AML) remain elusive. Utilizing a comprehensive approach, the researchers quantified METTL1/WDR4 expression levels through qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets.
Their findings reveal a significant elevation of METTL1/WDR4 in AML patients, correlating with poor prognosis. Functional assays involving METTL1 knockdown demonstrated a substantial reduction in cell proliferation and increased apoptosis in AML cells. Mechanistically, METTL1 knockdown resulted in a significant decrease in m7G modification abundance on tRNA, destabilizing tRNAs and facilitating the biogenesis of tsRNAs in AML cells. Profiling of nascent proteins further unveiled that METTL1 knockdown and transfection of total tRNAs isolated from METTL1 knockdown AML cells decreased global translation efficiency.
In conclusion, their study delineates the crucial role of METTL1/WDR4 in AML leukemogenesis, highlighting their potential as promising therapeutic targets for AML therapy. The comprehensive insights provided contribute to a deeper understanding of the intricate molecular mechanisms underlying AML pathogenesis, paving the way for targeted interventions in the clinical management of this disease.
Source: ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00477-8
