NDLI: METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control

Content Provider	Springer Nature : BioMed Central
Author	Zhao, Pan Xia, Lin Chen, Dan Xu, Wei Guo, Huanping Xu, Yinying Yan, Bingbing Wu, Xiao Li, Yuxia Zhang, Yunfang Zhang, Xi
Abstract	Background RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. Methods METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC–MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements. Results METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells. Conclusions Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.
Related Links	https://ehoonline.biomedcentral.com/counter/pdf/10.1186/s40164-024-00477-8.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	21623619
DOI	10.1186/s40164-024-00477-8
Journal	Experimental Hematology & Oncology
Issue Number	1
Volume Number	13
Language	English
Publisher	BioMed Central
Publisher Date	2024-01-24
Access Restriction	Open
Subject Keyword	Hematology Oncology Cancer Research METTL1/WDR4 tRNA modification m7G AML Translation control
Content Type	Text
Resource Type	Article
Subject	Hematology Oncology Cancer Research
Journal Impact Factor	9.4/2023
5-Year Journal Impact Factor	8.3/2023

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