June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Characterization of a new RNA-binding protein Rbm24 in vertebrate eye development
Author Affiliations & Notes
  • Soma Dash
    Biological Sciences, University of Delaware, Newark, Delaware, United States
  • Melinda K Brastrom
    Department of Biology, University of Iowa, Iowa City, Iowa, United States
  • Diane Slusarski
    Department of Biology, University of Iowa, Iowa City, Iowa, United States
  • Salil Lachke
    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   Soma Dash, None; Melinda Brastrom, None; Diane Slusarski, None; Salil Lachke, None
  • Footnotes
    Support  NIH/NEI R01 EY021505, The Pew Charitable Trusts Scholars Program in Biomedical Sciences
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1209. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Soma Dash, Melinda K Brastrom, Diane Slusarski, Salil Lachke; Characterization of a new RNA-binding protein Rbm24 in vertebrate eye development. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1209.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Recently we described three conserved RNA-binding proteins (RBPs) Tdrd7, Celf1 and Caprin2 that function in vertebrate lens development – findings that serve to indicate the importance of post-transcriptional control of gene expression in ocular cell differentiation. However, the significance of RBPs in early eye development remains unclear. Using the bioinformatics tool iSyTE (integrated Systems Tool for Eye gene discovery) we have identified a new RBP Rbm24 (RNA binding motif protein 24) whose expression is conserved in vertebrate eye development and suggestive of function in this process. In agreement with this prediction, we find that deficiency of Rbm24 in mouse and fish causes eye defects.

Methods : Targeted Rbm24 knockout mouse mutants and rbm24a morpholino-knockdown zebrafish morphants were generated and analyzed for eye abnormalities. Immunostaining with eye markers was performed to characterize ocular tissue. RNA immunoprecipitation (RIP) using Rbm24 antibody followed by RT-qPCR on mouse eye tissue was carried out to investigate Rbm24-associated RNA targets. TUNEL assay was performed to examine defects in apoptosis.

Results : Rbm24-/- mice exhibit unilateral anophthalmia (50% penetrance) and microphthalmia (100% penetrance) beginning at embryonic day (E) 11.5. rbm24a-knockdown in zebrafish causes microphthalmia. TUNEL assay suggests that Rbm24-/- mice exhibit apoptosis defects. Interestingly, severe down-regulation of the anophthalmia-linked protein Sox2 was observed in the optic vesicle and the overlying surface ectoderm in Rbm24-/- mice. Further, a second transcription factor involved in early eye development, Lhx2, as well as markers of lens epithelium (E-cad) and fibers (gamma-crystallin) were also found to be down-regulated in Rbm24-/- ocular tissue. RIP assays indicated that Rbm24 binds directly to Sox2 and Lhx2 transcripts in wild-type E14.5 mouse eye tissue, suggesting that Rbm24 mediates direct control of key regulators in the eye.

Conclusions : We have identified a new RBP Rbm24 that functions in early eye development in vertebrates. Rbm24 regulates expression of the transcription factor Sox2, among other important ocular proteins, and its deficiency results in anophthalmia, microphthalmia and lens defects. In light of recent findings on other RBPs, these data suggest that conserved post-transcriptional gene expression regulators have evolved to control eye development in vertebrates.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×