Abstract
Abstract Submission
The abstract submission site for the 2023 ICL will be open beginning August 1, 2023. Please note the following abstract submission instructions:
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Applying iSyTE to uncover regulatory networks in lens development and its associated defects
Salil A. Lachke1,2, Sandeep Aryal1, Sarah Coomson1, Sanjaya Shrestha1, Deepti Anand1
1Department of Biological Sciences, University of Delaware, Newark, DE, USA
2Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE, USA
Purpose: The development and maintenance of lens transparency involves modulation of gene expression control in epithelial and fiber cells. Many genes, for example crystallins, are transcribed at high levels in fiber cells. However, it is unknown whether transcription in fiber cells involves lens-specialized function of components of the “general” transcription machinery to achieve the extremely high levels of such mRNAs. Further, stability and/or translation of lens-expressed mRNAs need to be controlled by post-transcriptional mechanisms to achieve optimal transcriptome and proteome in epithelial and fiber cells. Here, we apply the bioinformatics tool iSyTE to identify the transcription elongation factor Ell2 and the RNA-binding protein (RBP) Elavl1 that are involved in orchestrating these events in the lens.
Methods: Lens-specific compound conditional deletion mice for Elavl1 and Ell2 were generated using Pax6GFPCre and termed Elavl1cKO and Ell2cKO, respectively. Lens tissue from cKO mice was characterized by immunostaining, RNA-sequencing (RNA-seq) and RT-qPCR.
Results: Elavl1cKO and Ell2cKO lenses exhibit morphological defects that are detected in embryonic and early postnatal stages, respectively. RNA-seq identifies mis-expression of many genes in both cKO lenses. El12cKO lenses show significantly reduced transcript levels of a cohort of fiber-expressed genes such as crystallins, while Elavl1cKO lenses show abnormal mRNA levels of several novel factors in the lens, as well those with known function in the lens.
Conclusion: These data demonstrate that the new iSyTE-predicted genes, the RBP Elavl1, and transcription elongation factor Ell2, mediate regulation of key genes in lens development, and provide new insights into the molecular pathology of cataract and lens defects in animals deficient in these genes. Importantly, Ell2 is found to be mis-expressed in mouse cKO lenses for the RBPs Elavl1 and Celf1, suggesting a crosstalk between transcriptional and post-transcriptional regulatory networks that governs optimal transcriptome and proteome in the lens.