RNA‐binding proteins in eye development and disease: implication of conserved RNA granule components

Abstract

The molecular biology of metazoan eye development is an area of intense investigation. These efforts have led to the surprising recognition that although insect and vertebrate eyes have dramatically different structures, the orthologs or family members of several conserved transcription and signaling regulators such as Pax6, Six3, Prox1 and Bmp4 are commonly required for their development. In contrast, our understanding of post-transcriptional regulation in eye development and disease, particularly regarding the function of RNA binding proteins (RBPs), is limited. We examine the present knowledge of RBPs in eye development in the insect model Drosophila, as well as several vertebrate models such as fish, frog, chicken and mouse. Interestingly, of the 42 RBPs that have been investigated with for their expression or function in vertebrate eye development, 24 (~60%) are recognized in eukaryotic cells as components of RNA granules such as Processing bodies (P-bodies), Stress granules, or other specialized ribonucleoprotein (RNP) complexes. We discuss the distinct developmental and cellular events that may necessitate potential RBP/RNA granule-associated RNA regulon models to facilitate post-transcriptional control of gene expression in eye morphogenesis. In support of these hypotheses, three RBPs and RNP/RNA granule components Tdrd7, Caprin2 and Stau2 are linked to ocular developmental defects such as congenital cataract, Peters anomaly and microphthalmia in human patients or animal models. We conclude by discussing the utility of interdisciplinary approaches such as the bioinformatics tool iSyTE (integrated Systems Tool for Eye gene discovery) to prioritize RBPs for deriving post-transcriptional regulatory networks in eye development and disease.

Rbm24 controls poly(A) tail length and translation efficiency of crystallin mRNAs in the lens via cytoplasmic polyadenylation

“…This may represent a general function of Rbm24 in regulating various differentiation processes. Because of the implication of RBPs in eye development and disease (53) and the similarities in structure and regulation between zebrafish and human lenses (54), understanding the posttranscriptional mechanisms that help to produce high levels of transparent proteins in the lens could open novel perspectives for the prevention and treatment of cataracts. Furthermore, given the highly conserved expression of vertebrate Rbm24 in the lens, it will be particularly interesting to identify human mutations affecting the cis-regulatory elements that disrupt its lens-specific expression and lead to congenital cataracts.…”

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

“…On the other hand, modulation of other cell cytoprotective mechanisms, such as autophagy, including specific organelle-phagy [57] and mitochondrial dynamics [53], or the regulation of SG generation in the retina [141], may provide potential cytoprotective strategies for IRD treatment.…”

The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development

“…These events are collectively defined as post-transcriptional control of gene expression and are essential to determine the proteome of a cell. While the role of transcription factors in vertebrate organogenesis is established–for example, a detailed transcriptional regulatory network governing lens development is now derived [ 2 ]–that of RBPs, functioning in post-transcriptional gene expression control, is not well defined [ 3 ]. This represents a significant knowledge gap, especially considering that vertebrate genomes encode similar numbers of transcription factors and RBPs [ 4 ].…”