WTAP tetramer ensures m6A writer assembly and faithful mitosis.

The m6A methyltransferase complex ("writer") regulates mRNA stability and translation, but how its assembly is orchestrated remains incompletely understood. Wilms' tumor 1-associating protein (WTAP) is a conserved regulatory subunit essential for m6A deposition and cell proliferation, yet its structural organization and mechanistic contributions remain elusive. Here, we report that WTAP dimerizes and further assembles into a stable tetramer through its middle coiled-coil domain, as revealed by high-resolution crystal structures. Disruption of this tetrameric interface abolishes WTAP's interaction with METTL3, METTL14, and ZC3H13, impairs m6A deposition, and fails to rescue proliferation defects in WTAP-depleted cells. Live-cell imaging demonstrates that WTAP is required for accurate chromosome segregation, and MeRIP-seq analysis identifies WTAP-dependent m6A regulation as a critical determinant sustaining the expression of mitotic regulators, including KIF20A. Together, our study defines a tetrameric scaffold function for WTAP that is essential for writer complex integrity and highlights its pivotal role in linking m6A methylation to cell cycle progression.