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Deepti Anand, Carrie E Barnum, Salil Anil Lachke; Identification of abnormally expressed miRNAs in Tdrd7 null mouse lens. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3061.
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© ARVO (1962-2015); The Authors (2016-present)
Tdrd7 exhibits conserved expression in lens development and its deficiency causes early-onset cataracts in human, mouse and chicken. Tdrd7 encodes a tudor domain protein that also contains OST-HTH/LOTUS domains, which are implicated in RNA binding. Here, we investigated whether Tdrd7 deficiency leads to mis-regulation of miRNAs in the lens. We report the analysis of genome-wide miRNA profiling in Tdrd7 null mouse lens.
Genome-wide miRNA expression profiling of Tdrd7 null and control mouse lenses at post-natal day (P)4 was performed using Affymetrix miRNA 3.0 arrays. The datasets were background corrected and normalized using R packages Affy and limma, followed by linear model fit using lmfit. Comparative analysis of Tdrd7 null and control samples identified differentially expressed miRNAs at significant p-values (p<0.05). miRNA-mRNA target predictions and functional annotations were performed using MirTarget integrated in the miRDB resource, as well as with the DAVID bioinformatics tool.
miRNA microarray profiling of Tdrd7 null and control lens tissue identified eight miRNAs that exhibit significantly reduced expression upon Tdrd7 deficiency. These are let-7b, miR-34c, miR-298, miR-382, miR-409, miR-1198, miR-1947 and miR-3092. Further, this analysis identified fourteen miRNAs that are up-regulated in the mutant lens. These are miR-15a, miR19a, miR138, miR-328, miR-339, miR-345, miR-378, miR-384, miR-467a, miR-1224, miR-1935, miR-1946a, miR3102 and miR-3107. Computational analysis of the predicted mRNA targets for these differentially expressed miRNAs reveals a statistically significant enrichment of gene ontology categories for “eye development”, “DNA-binding”, “RNA-binding”, “alternative splicing” and “transcription regulation”. Further analysis identified a significant correlation between the expression patterns of the differentially expressed miRNAs and their predicted mRNA targets in Tdrd7 null lens microarray and RNA-seq datasets. Finally, miRNA microarray profiling of P4 control lens also validates previously identified highly expressed lens miRNAs, such as miR-184, miR-26a, let-7b, let-7c, miR-204 and miR-125b.
This study identifies 22 miRNAs that are significantly mis-regulated in the Tdrd7 null lens and predicts their mRNA targets, in the process further supporting Tdrd7 function in mediating post-transcriptional control of gene expression in the lens.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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