The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer.

Abstract

RNA can be modified by over 170 types of distinct chemical modifications, and the most abundant internal modification of mRNA in eukaryotes is N6-methyladenosine (m⁶A). The m⁶A modification accelerates mRNA process, including mRNA splicing, translation, transcript stability, export and decay. m⁶A RNA modification is installed by methyltransferase-like proteins (writers), and potentially removed by demethylases (erasers), and this process is recognized by m⁶A-binding proteins (readers). Notably, alterations of m⁶A-modified proteins (writers, erasers and readers) are involved in the tumorigenesis, progression and metastasis. Importantly, the fate of m⁶A-methylated mRNA is mediated mostly through m⁶A readers, and among these readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are unique RNA-binding proteins (RBPs) that stabilize their targets mRNA via m⁶A modification. In this review, we update the writers, erasers and readers, and their cross-talks in m⁶A modification, and briefly discuss the oncogenic role of IGF2BPs in cancer. Most importantly, we mainly review the up-to-date knowledges of IGF2BPs (IGF2BP1/2/3) as m⁶A readers in an m⁶A-modified manner in cancer progression.