m⁶A reader Igf2bp3 enables germ plasm assembly by m⁶A-dependent regulation of gene expression in zebrafish

Bucky ball (Buc) is involved in germ plasm (GP) assembly during early zebrafish development by regulating GP mRNA expression via an unknown mechanism. The present study demonstrates that an m⁶A reader Igf2bp3 interacts and colocalizes with Buc in the GP. Similar to the loss of Buc, the genetic deletion of maternal igf2bp3 in zebrafish leads to abnormal GP assembly and insufficient germ cell specification, which can be partially restored by the injection of igf2bp3 mRNA. Igf2bp3 binds to m⁶A-modified GP-organizer and GP mRNAs in an m⁶A-dependent manner and prevents their degradation. These findings indicate that the functions of Igf2bp3, a direct effector protein of Buc, in GP mRNA expression and GP assembly involve m⁶A-dependent regulation; these results emphasize a critical role of m⁶A modification in the process of GP assembly.