Sophisticated Gene Regulation for a Complex Physiological System: The Role of Non-coding RNAs in Photoreceptor Cells

Abstract

Photoreceptors (PRs) are specialized neuroepithelial cells of the retina responsible for sensory transduction of light stimuli. In the highly structured vertebrate retina, PRs have a highly polarized modular structure to accommodate the demanding processes of phototransduction and the visual cycle. Because of their function, PRs are exposed to continuous cellular stress. PRs are therefore under pressure to maintain their function in defiance of constant environmental perturbation, besides being part of a highly sophisticated developmental process. All this translates into the need for tightly regulated and responsive molecular mechanisms that can reinforce transcriptional programs. It is commonly accepted that regulatory non-coding RNAs (ncRNAs), and in particular microRNAs (miRNAs), are not only involved but indeed central in conferring robustness and accuracy to developmental and physiological processes. Here we integrate recent findings on the role of regulatory ncRNAs (e.g., miRNAs, lncRNAs, circular RNAs, and antisense RNAs), and of their contribution to PR pathophysiology. We also outline the therapeutic implications of translational studies that harness ncRNAs to prevent PR degeneration and promote their survival and function.

New hypotheses of cell type diversity and novelty from comparative single cell and nuclei transcriptomics in echinoderms

“…Finally, Pmin CL 22 was marked by genes related to a diverse range of sensory capabilities such as mechanosensing (degenerin mec-4 ( MEC4 , adjusted p-value = 3.06E-19) (O’Hagan et al, 2005) and photosensing (TUB like protein 4 ( tulp4 , adjusted p-value =0.01641617)) (Carrella et al, 2020).…”

“…This cluster was also represented by high levels of the transcription factor Paired box protein Pax5-like (Pax5L, adjusted p-value =4.07E-299 ), which was also shown via WMISH to express in cells embedded in the ectoderm (Figure 5.E). Finally, Pmin CL 22 was marked by genes related to a diverse range of sensory capabilities such as mechanosensing (degenerin mec-4 (MEC4, adjusted p-value = 3.06E-19) (O'Hagan et al, 2005) and photosensing (TUB like protein 4 (tulp4, adjusted p-value =0.01641617 )) (Carrella et al, 2020). Glial cells missing transcription factor-like (gcml), the sea star ortholog of the Drosophila glial cells missing (Dmel_CG12245), was also identified as a statistically significant marker gene of Pmin CL 22 (adjusted p-value = 1.04E-250).…”

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration

“…Additionally, in RNA-seq analysis, we identified common regulation ceRNA network including 3 DElncRNA (URS0000B28F2F, LOC100911498, URS0000B2E4CC), 5 DEmiRNA (novel-rno-miR-297-3p, rno-miR-425-3p, rno-miR-323-5p, rno-miR-3556a, rno-miR-181d-5p) and 109 DEmRNA between photoreceptor degenerations and control groups, suggesting the common ceRNA regulation network may facilitate the understanding of the mechanisms and benefit for the therapy in photoreceptor degeneration diseases. Several identified lncRNAs play crucial roles in neuron function and maintenance in neurodegenerative diseases, such as Tug1, participating in normal photoreceptor development and contributing to rod differentiation and survival ( Carrella et al, 2020 ), and Meg3, regulating the process of light-induced retinal damage ( Zhu et al, 2018 ). In our study, three lncRNAs (URS0000B28F2F, LOC100911498 and URS0000B2E4CC) we screened were significantly upregulated in photoreceptor degeneration models.…”

Epigenetic Switches in Retinal Homeostasis and Target for Drug Development

“…They fine-tune gene expression by binding to target mRNAs, affecting translation and stability. Accumulating evidence indicates that non-coding RNAs are essential for retinal development, cell fate determination, and response to injury [ 27 , 28 ].…”