An oncopeptide regulates m(6)A recognition by the m(6)A reader IGF2BP1 and tumorigenesis

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 RBRP(high) have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m(6)A readers and strengthens m(6)A recognition on the target RNAs by the m(6)A reader to exert its oncogenic functions.