N6-methyladenosine (m6A) is a prevalent and reversible modification in mammalian RNAs. This study reports that human METTL14 catalyzes m6A RNA methylation, and together with METTL3, forms a stable heterodimer core complex (METTL3-14) that functions in cellular m6A deposition on nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect m6A methylation. The METTL3-14 complex exhibits synergistic methylation activity, preferentially methylating RNA substrates containing the consensus sequence GGACU. In HeLa cells, knockdown of METTL3, METTL14, or WTAP significantly reduces m6A levels and increases mRNA degradation, indicating a negative impact on gene expression. PAR-CLIP analysis reveals that the METTL3-14 complex binds to intergenic regions and introns, with a significant overlap with m6A-containing genes. These findings provide insights into the regulation of m6A methylation and its biological functions.N6-methyladenosine (m6A) is a prevalent and reversible modification in mammalian RNAs. This study reports that human METTL14 catalyzes m6A RNA methylation, and together with METTL3, forms a stable heterodimer core complex (METTL3-14) that functions in cellular m6A deposition on nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect m6A methylation. The METTL3-14 complex exhibits synergistic methylation activity, preferentially methylating RNA substrates containing the consensus sequence GGACU. In HeLa cells, knockdown of METTL3, METTL14, or WTAP significantly reduces m6A levels and increases mRNA degradation, indicating a negative impact on gene expression. PAR-CLIP analysis reveals that the METTL3-14 complex binds to intergenic regions and introns, with a significant overlap with m6A-containing genes. These findings provide insights into the regulation of m6A methylation and its biological functions.