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

Abstract 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.