Abstract
BackgroundThe molecular complexity of neural retina development remains poorly studied. Knowledge of retinal neurogenesis regulation sheds light on retinal degeneration therapy exploration. Therefore, we integrated the time-series circRNA, lncRNA, miRNA, and mRNA expression profiles of the developing retina through whole-transcriptome sequencing. The key functional ncRNAs and the ceRNA network regulating retinal neurogenesis were identified.ResultsTranscriptomic analysis identified circRNA as the most variable ncRNA subtype. We screened a series of neurogenesis-related circRNAs, lncRNAs, and miRNAs using different strategies based on their diversified molecular functions. The expression of circCDYL, circATXN1, circDYM, circPRGRIP, lncRNA Meg3, and lncRNA Vax2os was validated by quantitative real-time PCR. These circRNAs and lncRNAs participate in neurotransmitter transport and multicellular organism growth through the intricate circRNA/lncRNA-miRNA-mRNA network.ConclusionWhole-transcriptome sequencing and bioinformatics analysis systematically screened key ncRNAs in retinal neurogenesis. The validated ncRNAs and their circRNA/lncRNA-miRNA-mRNA network involve neurotransmitter transport and multicellular organism growth during retinal development.
Highlights
The molecular complexity of neural retina development remains poorly studied
The annotations showed that most Long non-coding RNA (lncRNA)-seq and Circular RNA (circRNA)-seq reads could be mapped to coding DNA sequences (CDSs), and Micro RNA (miRNA) were the dominant class of small RNAs in small RNA sequencing (Supplementary Fig. 1)
Through single time-series differential expression analysis, we identified 10,336 mRNAs, 1755 lncRNAs, 17,468 circRNAs, and 649 miRNAs across six time points of development (Fig. 1f-i)
Summary
The molecular complexity of neural retina development remains poorly studied. Knowledge of retinal neurogenesis regulation sheds light on retinal degeneration therapy exploration. We integrated the timeseries circRNA, lncRNA, miRNA, and mRNA expression profiles of the developing retina through whole-transcriptome sequencing. The key functional ncRNAs and the ceRNA network regulating retinal neurogenesis were identified. Its development process consists of multistage cell proliferation and differentiation with delicate control of spatiotemporal gene expression [2, 3]. Any perturbation in the gene regulatory network may bring about a cascade effect, disturbing retinal development and inducing visual loss [4]. Knowledge of gene expression regulation is the kernel of the development process, which. Noncoding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, play vital roles in physiological retinal development, homeostasis, and function [5, 6]. MiRNAs can regulate gene expression by degrading mRNAs with corresponding miRNA response elements (MREs) [7]. Torre et al discovered that three miRNAs, let-7, miR-125, and miR-9, are indispensable for progenitor identity maintenance during retinal
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