Abstract

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that play an important role in the control of fundamental biological processes in both physiological and pathological conditions. Their function in retinal cells is just beginning to be elucidated, and a few have been found to play a role in photoreceptor maintenance and function. MiR-211 is one of the most abundant miRNAs in the developing and adult eye. However, its role in controlling vertebrate visual system development, maintenance and function so far remain incompletely unexplored. Here, by targeted inactivation in a mouse model, we identify a critical role of miR-211 in cone photoreceptor function and survival. MiR-211 knockout (−/−) mice exhibited a progressive cone dystrophy accompanied by significant alterations in visual function. Transcriptome analysis of the retina from miR-211−/− mice during cone degeneration revealed significant alteration of pathways related to cell metabolism. Collectively, this study highlights for the first time the impact of miR-211 function in the retina and significantly contributes to unravelling the role of specific miRNAs in cone photoreceptor function and survival.

Highlights

  • MicroRNAs are key post-transcriptional regulators of gene expression that play an important role in the control of fundamental biological processes in both physiological and pathological conditions

  • By RNA in situ hybridization (ISH), we showed that the expression of miR-211 is abundant in the developing eye and is detected in the presumptive retinal pigment epithelium (RPE), ciliary body, distal region of the developing retina of the optic cup recapitulating the expression of its host gene, the melastatin, transient receptor potential cation channel subfamily M member 1 (Trpm1) gene (Supplementary Fig. 1)

  • MiR-211 is expressed in the RPE and in the Inner Nuclear Layer (INL) with a weaker expression detected in the Outer Nuclear Layer (ONL) and in the Ganglion Cell Layer (GCL) as previously reported[26] (Supplementary Fig. 2c,d), again recapitulating the expression pattern of its host gene[27]

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Summary

Introduction

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that play an important role in the control of fundamental biological processes in both physiological and pathological conditions. Their function in retinal cells is just beginning to be elucidated, and a few have been found to play a role in photoreceptor maintenance and function. MicroRNAs (miRNAs) are a class of 20- to 25-nucleotide small noncoding RNA molecules that have basic roles in post-transcriptional regulation of gene expression and represent key players in the control of fundamental biological processes in both physiological and pathological conditions[9]. The consequences of the lack of single miRNAs with respect to photoreceptor maintenance and survival are still unknown

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