Putative RNA-binding regulatory peptide
positive regulation of mRNA binding
An oncopeptide regulates m<sup>6</sup>A recognition by the m<sup>6</sup>A reader IGF2BP1 and tumorigenesis.
N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent modification in eukaryotic RNAs. The biological importance of m<sup>6</sup>A relies on m<sup>6</sup>A readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of m<sup>6</sup>A readers are involved in the m<sup>6</sup>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<sup>6</sup>A reader IGF2BP1, and is thus named "RNA-binding regulatory peptide" (RBRP). RBRP binds to IGF2BP1 and strengthens m<sup>6</sup>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<sup>high</sup> have a poor prognosis. Thus, the oncopeptide RBRP encoded by LINC00266-1 is a regulatory subunit of m<sup>6</sup>A readers and strengthens m<sup>6</sup>A recognition on the target RNAs by the m<sup>6</sup>A reader to exert its oncogenic functions.