Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 5;30(1):69-85.e7.
doi: 10.1016/j.stem.2022.12.003. Epub 2022 Dec 26.

Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance

Ying Cheng  1 , Zhuying Gao  1 , Tiantian Zhang  1 , Yuhua Wang  2 , Xueqin Xie  3 , Guoqiang Han  3 , Yashu Li  3 , Rong Yin  4 , Yilin Chen  5 , Peipei Wang  3 , Jin Hu  3 , Tong Zhang  3 , Chengli Guo  2 , Jihua Chai  2 , Jing Wang  2 , Manman Cui  3 , Kexin Gao  3 , Weidong Liu  2 , Shuxin Yao  3 , Pengbo Lu  3 , Ziyan Cao  3 , Yanbing Zheng  3 , Jiwei Chang  2 , Zheming Liu  6 , Qibin Song  6 , Weiming Li  5 , Fuling Zhou  4 , Haojian Zhang  7
Affiliations
Free article

Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance

Ying Cheng et al. Cell Stem Cell. .
Free article

Abstract

N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.

Keywords: IGF2BP2; PRMT6; RNA m(6)A; acute myeloid leukemia; leukemia stem cells.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Comment in

Publication types