Dynamic Landscape of Alternative Polyadenylation during Retinal Development

The development of the central nervous system (CNS) is a complex process that must be exquisitely controlled at multiple levels to ensure the production of appropriate types and quantity of neurons. RNA alternative polyadenylation (APA) contributes to transcriptome diversity and gene regulation and has recently been shown to be widespread in the CNS. However, previous studies have been primarily focused on the tissue specificity of APA and developmental APA change of whole model organisms, a systematic survey of APA usage is lacking during CNS development. Here we conducted global analysis of APA during mouse retinal development, and identified stage-specific polyadenylation (pA) sites that are enriched for genes critical for retinal development and visual perception. Moreover, we demonstrated 3'UTR lengthening and increased usage of intronic pA sites over development that would result in gaining many different RBP (RNA binding protein) and miRNA target sites. Furthermore, we showed that a considerable number of polyadenylated lncRNAs are co-expressed with protein-coding genes involved in retinal development and functions. Together, our data indicate that APA is highly and dynamically regulated during retinal development and maturation, suggesting that APA may serve as a crucial mechanism of gene regulation underlying the delicate process of CNS development. Overall design: PA-seq of mouse retina tissues at embryonic day E13.5, E15.5, E18.5 and postnatal day P0, P6, P21

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Hu W, Li S, Park JY, Boppana S, Ni T, Li M, Zhu J, Tian B, Xie Z, Xiang M