September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Identification of abnormally expressed miRNAs in Tdrd7 null mouse lens
Author Affiliations & Notes
  • Deepti Anand
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Carrie E Barnum
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Salil Anil Lachke
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States
    Center for Bioinformatics and Computational Biology, University of Delaware, Newark, Delaware, United States
  • Footnotes
    Commercial Relationships   Deepti Anand, None; Carrie Barnum, None; Salil Lachke, None
  • Footnotes
    Support  NIH/NEI R01 EY021505, The Pew Charitable Trusts Scholars Program in Biomedical Sciences
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3061. doi:
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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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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