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Prediction of microRNAs affecting mRNA expression during retinal development

Arora, A; Guduric-Fuchs, J; Harwood, L; Dellett, M; Cogliati, T; Simpson, DA; (2010) Prediction of microRNAs affecting mRNA expression during retinal development. BMC Developmental Biology , 10 , Article 1. 10.1186/1471-213X-10-1. Green open access

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Abstract

Background: MicroRNAs (miRNAs) are small RNA molecules (similar to 22 nucleotides) which have been shown to play an important role both in development and in maintenance of adult tissue. Conditional inactivation of miRNAs in the eye causes loss of visual function and progressive retinal degeneration. In addition to inhibiting translation, miRNAs can mediate degradation of targeted mRNAs. We have previously shown that candidate miRNAs affecting transcript levels in a tissue can be deduced from mRNA microarray expression profiles. The purpose of this study was to predict miRNAs which affect mRNA levels in developing and adult retinal tissue and to confirm their expression.Results: Microarray expression data from ciliary epithelial retinal stem cells (CE-RSCs), developing and adult mouse retina were generated or downloaded from public repositories. Analysis of gene expression profiles detected the effects of multiple miRNAs in CE-RSCs and retina. The expression of 20 selected miRNAs was confirmed by RT-PCR and the cellular distribution of representative candidates analyzed by in situ hybridization. The expression levels of miRNAs correlated with the significance of their predicted effects upon mRNA expression. Highly expressed miRNAs included miR-124, miR-125a, miR-125b, miR-204 and miR-9. Over-expression of three miRNAs with significant predicted effects upon global mRNA levels resulted in a decrease in mRNA expression of five out of six individual predicted target genes assayed.Conclusions: This study has detected the effect of miRNAs upon mRNA expression in immature and adult retinal tissue and cells. The validity of these observations is supported by the experimental confirmation of candidate miRNA expression and the regulation of predicted target genes following miRNA over-expression. Identified miRNAs are likely to be important in retinal development and function. Misregulation of these miRNAs might contribute to retinal degeneration and disease. Conversely, manipulation of their expression could potentially be used as a therapeutic tool in the future.

Type: Article
Title: Prediction of microRNAs affecting mRNA expression during retinal development
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1471-213X-10-1
Publisher version: http://dx.doi.org/10.1186/1471-213X-10-1
Language: English
Additional information: © 2010 Arora et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: CENTRAL-NERVOUS-SYSTEM, REAL-TIME PCR, STEM-CELLS, GENE-EXPRESSION, MICROARRAY ANALYSIS, ANIMAL DEVELOPMENT, PROTEIN-SYNTHESIS, MIRNA EXPRESSION, MOUSE RETINA, C-ELEGANS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/132127
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