An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis
An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis
复制标题
癌肽调节 m(6)A 读取器 IGF2BP1 的 m(6)A 识别和肿瘤发生
DOI：
10.1038/s41467-020-15403-9
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发表时间：
2020-04-03
影响因子：
16.6
通讯作者：
Yan, Guang-Rong
中科院分区：
文献类型：
--
作者：
Zhu, Song;Wang, Ji-Zhong;Yan, Guang-Rong
N-6-甲基腺苷（m（6）A）是真核生物RNA中最常见的修饰。m（6）A的生物学重要性依赖于m（6）A阅读器，其控制mRNA的命运和功能。然而，m（6）A阅读器的其他调节亚基是否参与m（6）A在RNA上的识别仍然未被探索。在这里，我们发现长非编码RNA（lncRNA）LINC 00266 -1编码一个71个氨基酸的肽。该肽主要与RNA结合蛋白相互作用，包括m（6）A阅读器IGF 2BP 1，因此被命名为“RNA结合调节肽”（RBRP）。RBRP与IGF 2BP 1结合，并增强IGF 2BP 1对RNA（如c-Myc mRNA）的m（6）A识别，以增加mRNA的稳定性和c-Myc的表达，从而促进肿瘤发生。RBRP高的癌症患者预后差。因此，LINC 00266 -1编码的癌肽RBRP是m（6）A阅读器的调节亚基，并增强m（6）A阅读器对靶RNA的m6 A识别，以发挥其致癌功能。
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.