Specific regulation of m6A by SRSF7 promotes the progression of glioblastoma

Aberrant regulation of N6-methyladenosine (m6A) RNA methylation is important for various diseases. Based on integrative co-methylation network analysis, we previously revealed widespread specific regulation of m6A by RNA binding proteins (RBPs) to establish the cell-specific methylomes. However, whether these RBP-mediated specific regulation of m6A has important functions is not clear. Here, we found a glioma related m6A module in our previously established co-methylation network. From the potential regulators of this module, we identified the Serine/arginine factor 7 (SRSF7), an RBP associated with worse prognosis of glioblastoma patients, can specifically facilitate the m6A methylation near its binding sites on RNAs through recruiting methyltransferase complex. SRSF7 does not change the global m6A level but highly specifically promotes the m6A on genes involved in cell proliferation and migration. We then found SRSF7 and METTL3 promote the proliferation and migration of glioblastoma cells depend on each other. Finally, we found the effects of SRSF7 on glioblastoma cells was partially mediated by the two single-nucleotide m6A sites on PBK through recognition by IGF2BP2. Our study indicates that RBP-mediated specific regulation of m6A also plays important functional roles and sheds new light on the studies looking for m6A drug targets with less side effects.