Oscillatory Behaviors of microRNA Networks: Emerging Roles in Retinal Development

Abstract

A broad repertoire of transcription factors and other genes display oscillatory patterns of expression, typically ranging from 30 min to 24 h. These oscillations are associated with a variety of biological processes, including the circadian cycle, somite segmentation, cell cycle, and metabolism. These rhythmic behaviors are often prompted by transcriptional feedback loops in which transcriptional activities are inhibited by their corresponding gene target products. Oscillatory transcriptional patterns have been proposed as a mechanism to drive biological clocks, the molecular machinery that transforms temporal information into accurate spatial patterning during development. Notably, several microRNAs (miRNAs) -small non-coding RNA molecules-have been recently shown to both exhibit rhythmic expression patterns and regulate oscillatory activities. Here, we discuss some of these new findings in the context of the developing retina. We propose that miRNA oscillations are a powerful mechanism to coordinate signaling pathways and gene expression, and that addressing the dynamic interplay between miRNA expression and their target genes could be key for a more complete understanding of many developmental processes.

Light-Responsive MicroRNAs in Human Retinal Tissue are Differentially Regulated by Distinct Wavelengths of Light

“…We compared the generated NGS data with a previously published list of retina-specific miRNAs. 19 We detected 56 miRNAs (out of 60) that have been previously reported to be expressed in the developing retina (Figure 2A) . These 56 miRNAs represent approximately 67% of all mapped miRNA reads in human retinal organoids.…”

“…We showed that retinal organoids express a number of retina-specific miRNA families and clusters that have been previously associated with the regulation of neuronal or retinal cell fate, including miR-9, let-7, miR-7, miR-26, and miR-125. 19 To study the light-regulated miRNAs, we developed a photostimulation system Cell LighteR and used it to stimulate the organoids with light of different wavelengths. We showed that retinal organoids are responsive to photostimulation at the miRNA transcriptional level, as evidenced by the altered expression of multiple miRNA families and clusters in response to light exposure.…”

MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early‐onset cataracts and congenital glaucoma

“…Changes in seed sequence, which is essential for the miRNA binding to the target mRNA, may lead to binding disruption and/or alterations to pre-miRNA processing. 27,28 Notably, the expression of both pre-miRNA, as well as processed -3p/-5p forms of the MIR204 n.37C>T variant was not affected when compared to the wild type, The miR-204 belongs to the group of recently characterised retinal-specific miRNAs 31,32 regulating important processes in the retina including phototransduction cascade and development of RPE, neural retina, ciliary body, and lens. Given the critical role of the miR-204 in the ocular development and function of the retina, it is not surprising that pathogenic variants in the MIR204 gene lead to severe eye defects.…”

Confirmation of theMIR204n.37C>T heterozygous variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early-onset cataracts and congenital glaucoma

“…The MIR204 belongs to the group of recently characterised retinal-specific miRNAs 20,21 regulating important processes in the retina including phototransduction cascade and development of RPE, neural retina, ciliary body, and lens. Given the critical role of the MIR204 in the ocular development and function of the retina, it is not surprising that pathogenic variants in the MIR204 gene lead to severe eye defects.…”