N⁶-adenosine methylation enhances nuclear mRNA export through METTL3 and NUP93

Nuclear export of messenger RNAs (mRNAs) through nuclear pore complexes (NPCs) is a critical step in gene expression. Although N⁶-adenosine methylation (m⁶A) has been implicated in this process, the underlying mechanism remains obscure. Here we demonstrate, using single-molecule imaging, that m⁶A markedly accelerates the nuclear export of messenger ribonucleoproteins (mRNPs) by increasing export efficiency and shortening export time through NPCs. We further show that the m⁶A methyltransferase METTL3 localizes at NPCs and functionally associates with the nucleoporin NUP93 to promote the efficient export of m⁶A-modified mRNPs. The disruption of this functional association between METTL3 and NUP93 substantially impairs overall mRNP export efficiency. Notably, a steroid-resistant nephrotic syndrome (SRNS)-associated NUP93 variant (c.1162C>T, p.Arg388Trp) fails to associate with METTL3, resulting in the defective nuclear export of key methylated mRNAs required for kidney function. Together, our findings define an m⁶A-METTL3-NUP93 regulatory axis for nuclear mRNA export with broad implications for human disease.