Domain associated with zinc fingers‐containing <scp>NF90</scp> ‐ <scp>NF45</scp> complex inhibits <scp> m ⁶ A </scp> modification of primary <scp>microRNA</scp> by suppressing <scp>METTL3</scp> /14 activity

N⁶-methyladenosine (m⁶A) modifications accelerate microRNA (miRNA) biogenesis by promoting the processing of m⁶A-modified primary miRNAs (pri-miRNAs). However, the regulatory mechanism of m⁶A modification of pri-miRNA remains unclear. Here, we found that NF90-NF45 acts as a negative regulator of the m⁶A modification of pri-miRNA by methyltransferase-like 3/14 (METTL3/14). Using overexpression constructs, METTL3/14 promoted the biogenesis of miR-7, whereas NF90-NF45 suppressed miR-7 biogenesis. METTL3/14 overexpression relieved the inhibition of miR-7 biogenesis by NF90-NF45. NF90-NF45 attenuated m⁶A modification of pri-mir-7-1 in vitro; however, it had no effect on the m⁶A modification of pri-mir-200a because of the lower binding affinity of pri-mir-200a to NF90. Furthermore, NF90-NF45 did not interact with METTL3/14, according to immunoprecipitation analysis. These findings suggest that the m⁶A modification of pri-miRNAs by METTL3/14 is regulated by NF90-NF45 competing for pri-miRNA binding.