An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis

被引：217
作者：
Zhu, Song [1 ]
Wang, Ji-Zhong [1 ]
Chen, De [1 ]
He, Yu-Tian [1 ]
Meng, Nan [1 ]
Chen, Min [1 ]
Lu, Rui-Xun [1 ]
Chen, Xin-Hui [1 ]
Zhang, Xiao-Lan [1 ]
Yan, Guang-Rong [1 ]
机构：
[1] Guangzhou Med Univ, Affiliated Hosp 3, State Key Lab Resp Dis, Biomed Res Ctr,Guangzhou Municipal & Guangdong Pr, Guangzhou 510150, Peoples R China
来源：
NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期
基金：
中国国家自然科学基金;
关键词：
EPITHELIAL-MESENCHYMAL TRANSITION; RNA; CANCER; STEM; METHYLATION; METASTASIS; STABILITY; PROTEIN; LNCRNA; CELLS;
D O I：
10.1038/s41467-020-15403-9
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
N-6-methyladenosine (m(6)A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m(6)A relies on m(6)A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m(6)A readers are involved in the m(6)A recognition on RNAs. Here we discover that the long noncoding RNA (lncRNA) LINC00266-1 encodes a 71-amino acid peptide. The peptide mainly interacts with the RNA-binding proteins, including the m(6)A reader IGF2BP1, and is thus named "RNA-binding regulatory peptide" (RBRP). RBRP binds to IGF2BP1 and strengthens m(6)A recognition by IGF2BP1 on RNAs, such as c-Myc mRNA, to increase the mRNA stability and expression of c-Myc, thereby promoting tumorigenesis. Cancer patients with RBRPhigh have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m(6)A readers and strengthens m6A recognition on the target RNAs by the m(6)A reader to exert its oncogenic functions.
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页数：14
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