N⁶-methyladenosine (m⁶A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m⁶A relies on m⁶A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m⁶A readers are involved in the m⁶A 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 m⁶A reader IGF2BP1, and is thus named “RNA-binding regulatory peptide” (RBRP). RBRP binds to IGF2BP1 and strengthens m⁶A 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^high have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m⁶A readers and strengthens m⁶A recognition on the target RNAs by the m⁶A reader to exert its oncogenic functions.

N ⁶ -甲基腺苷 (m ⁶ A) 是真核 RNA 中最普遍的修饰。m ⁶ A的生物学重要性依赖于控制 mRNA 命运和功能的m ⁶ A 阅读器。然而，m ⁶ A 阅读器的其他调节亚基是否参与RNA 上的 m ⁶ A 识别仍然是未知的。在这里，我们发现长链非编码 RNA (lncRNA) LINC00266-1编码 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IGF2BP1，因此被命名为“RNA结合调节肽”（RBRP）。RBRP 与 IGF2BP1 结合并增强 m ⁶的识别通过IGF2BP1上的RNA，如c-Myc的表达，以增加mRNA的稳定性和表达的c-Myc，从而促进肿瘤发生。RBRP^高的癌症患者预后较差。因此，由 LINC00266-1 编码的癌肽 RBRP是 m ⁶ A 阅读器的调节亚基，并增强了 m ⁶ A 阅读器对目标 RNA 的m ⁶ A 识别以发挥其致癌功能。