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

Abstract

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.

The involvement of long non-coding RNA (lncRNA) in the regulation of N⁶-methyladenosine (m⁶A) modification of RNA is unclear. Here, the authors show that LINC00266-1 encodes a peptide that binds to m⁶A reader, IGF2BP1 to enhance the recognition of m⁶A modified RNA transcripts and increase their stability.