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

Nat Commun. 2020 Apr 3;11(1):1685. doi: 10.1038/s41467-020-15403-9.

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 RBRPhigh 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Animals
  • Binding Sites
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Methylation
  • Mice
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA Processing, Post-Transcriptional / genetics*
  • RNA Stability / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Survival Analysis
  • Tissue Array Analysis
  • Xenograft Model Antitumor Assays

Substances

  • IGF2BP1 protein, human
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA-Binding Proteins
  • N-methyladenosine
  • Adenosine