一种癌肽调节 mA 识别由 mA 阅读器 IGF2BP1 和肿瘤发生。

An oncopeptide regulates mA recognition by the mA reader IGF2BP1 and tumorigenesis.

机构信息

Biomedicine Research Center, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.

出版信息

Nat Commun. 2020 Apr 3;11(1):1685. doi: 10.1038/s41467-020-15403-9.

N-methyladenosine (mA) is the most prevalent modification in eukaryotic RNAs. The biological importance of mA relies on mA readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of mA readers are involved in the mA 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 mA reader IGF2BP1, and is thus named "RNA-binding regulatory peptide" (RBRP). RBRP binds to IGF2BP1 and strengthens mA 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 RBRP have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of mA readers and strengthens mA recognition on the target RNAs by the mA reader to exert its oncogenic functions.

N6-甲基腺苷（m6A）是真核 RNA 中最普遍的修饰。m6A 的生物学重要性依赖于 m6A 读码器，它控制着 mRNA 的命运和功能。然而，m6A 读码器的其他调节亚基是否参与 RNA 上的 m6A 识别仍未被探索。在这里，我们发现长非编码 RNA（lncRNA）LINC00266-1 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 m6A 读码器 IGF2BP1，因此被命名为“RNA 结合调节肽”（RBRP）。RBRP 与 IGF2BP1 结合，增强 IGF2BP1 在 RNA 上对 m6A 的识别，如 c-Myc mRNA，从而增加 c-Myc mRNA 的稳定性和表达，促进肿瘤发生。具有 RBRP 的癌症患者预后不良。因此，由 LINC00266-1 编码的致癌肽 RBRP 是 m6A 读码器的调节亚基，通过 m6A 读码器增强对靶 RNA 上的 m6A 识别，从而发挥其致癌功能。