Imp/IGF2BP and Syp/SYNCRIP temporal RNA interactomes uncover combinatorial networks of regulators of Drosophila brain development.

Temporal patterning of neural progenitors is an evolutionarily conserved mechanism generating neural diversity. In Drosophila, postembryonic neurogenesis requires the RNA binding proteins (RBPs) Imp/IGF2BP and Syp/SYNCRIP. However, how they coachieve their function is not well understood. Here, we elucidate the in vivo temporal RNA interactome landscapes of Imp and Syp during larval brain development. Imp and Syp bind a highly overlapping set of conserved mRNAs encoding proteins involved in neurodevelopment. We identify transcripts differentially occupied by Imp/Syp over time, featuring a network of known and previously unknown candidate temporal regulators that are post-transcriptionally regulated by Imp/Syp. Furthermore, the physical and coevolutionary relationships between Imp and Syp binding sites reveal a combinatorial, rather than competitive, mode of molecular interplay. Our study establishes an in vivo framework for dissecting the temporal coregulation of RBP networks as well as providing a resource for understanding neural fate specification.