GSE112792
An Auts2-Containing RNA-Binding Complex Regulates Transcript Expression in Developing Cerebral Cortex
Molecular functions of the intellectual disability syndrome gene AUTS2 remain uncertain. Two mechanisms of Auts2 function have been proposed. One study found that Auts2 modifies Polycomb repressive complex 1 (PRC1) to activate transcription of target neurodevelopmental genes by recruiting EP300, a histone acetyltransferase. A second study found that cytoplasmic AUTS2 regulates cytoskeletal assembly through PREX1 to promote neurite outgrowth and migration. To further investigate Auts2 functions, we screened for AUTS2 interactors in cerebral cortex, and profiled changes of transcript expression in the developing cortex of Auts2 conditional mutant mice. AUTS2 immunoprecipitation experiments identified interactions with proteins involved in pre-mRNA processing, and mRNAs, including those encoding EP300 and PREX1, both bound by AUTS2-containing complexes and dysregulated in Auts2 mutant cortex. We propose that AUTS2 interacts with an RNA-binding complex that directly targets transcripts encoding Auts2 effectors. This mechanism provides a unifying model that accounts for previously disparate hypotheses of AUTS2 functions. Overall design: 4 Biological replicates of P0.5 C57Bl6/J Frontal Cortex, 4 Bioloigical Replicates of Auts2 Exon 15 Flx/Flx Emx1-cre conditional knockout. 2 Biological Replicates of P0.5 C57BL6/J Cortex split into Auts2 C-terminal Antibody RIP-Seq, IgG IP and 10% Input (6 samples total in matched trios)