Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.He...Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m^(6)A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m^(6)A methylation.We then indicate that SRSF7 is a novel m^(6)A regulator,which specifically facilitates the m^(6)A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase complex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m^(6)A methyltransferase.The two m^(6)A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m^(6)A and validates the presence and functional importance of temporal-and spatial-specific regulation of m^(6)A mediated by RNA-binding proteins(RBPs).展开更多
基金supported by the National Key R&D Program of China(Grant No.2018YFA0107200)to JWthe National Natural Science Foundation of China(Grant Nos.81830082,82030078,and 81621004 to JL+1 种基金Grant Nos.31771446 and 31970594 to JWGrant No.32100452 to XS).
文摘Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m^(6)A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m^(6)A methylation.We then indicate that SRSF7 is a novel m^(6)A regulator,which specifically facilitates the m^(6)A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase complex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m^(6)A methyltransferase.The two m^(6)A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m^(6)A and validates the presence and functional importance of temporal-and spatial-specific regulation of m^(6)A mediated by RNA-binding proteins(RBPs).
