Developmental profiling of RNA expression using PATseq identifies alternative polyadenylation as an important mechanism for the development of cerebral cortex neurons during mouse brain development. (#269)
Alternative polyadenylation is an important molecular feature of cellular mRNAs which influences gene expression and protein translation from mature transcripts. In this study, we have surveyed global polyadenylation during mouse brain development using PAT-seq, a cost-effective and high throughput technique to study 3’UTR length. We find dynamic changes to 3’UTR length across a variety of cellular mRNAs which are relevant to neurogenesis, neuronal differentiation and synapse development. When we focussed on a set of 14 cell migration genes which show dynamic polyadenylation during brain development, we discovered an enrichment in binding sites for poly(A) RNA binding proteins within their 3’UTRs. Guided by this insight, we then investigated the potential functional relevance of developmental changes to poly(A) binding in embryonic cortical neurons by performing in utero electroporation to knockdown the expression of poly(A) RNA binding factors Zc3h14 and Pabpn1 within E14.5-born cells. Through this approach, we found that suppression of each of these poly(A) binding factors impaired the development of embryonic cortical neurons in different ways. Thus, our study demonstrates that both polyadenylation, as well as the expression of specific poly(A) binding factors are critical to the development of cerebral cortex neurons during brain development.