# Post transcriptional control of gene expression in the lens

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2021 · $391,800

## Abstract

The eye lens is a transparent tissue that refracts and focuses light on the retina to allow clear vision. If the lens
loses its transparency, vision is impaired, and the disease is termed “cataract”. Cataract is the major cause of
blindness worldwide, commonly found in aged individuals (about half of Americans aged 80 or older develop
cataract), but can also be present at birth or develop in early childhood – termed pediatric cataract. Genetic
anomalies are estimated to account for about 25-50% of pediatric cataract cases, and the etiology of majority of
these are unknown. Importantly, while the role of signaling and transcription factors in lens development and
cataract have been well defined over the last few decades, that of proteins involved in post-transcriptional gene
expression control is grossly understudied – indeed, only four such proteins have been characterized so far in
the lens. Our efforts in characterizing these proteins have demonstrated that post-transcriptional regulatory
mechanisms are critical for lens development, and their loss results in early onset cataract and eye defects.
Identification of these factors was made possible by our novel bioinformatics approach iSyTE (integrated
Systems Tool for Eye gene discovery), which is effective in identifying high-priority target genes linked to lens
development and cataract. We have now used iSyTE to identify a new post-transcriptional regulator in the lens,
namely, Elavl1 (Embryonic lethal abnormal vision (ELAV) like RNA-binding protein). The function of Elavl1 has
not been examined in the lens. Therefore, we developed a new Elavl1-targeted lens-specific conditional knockout
(KO) mouse model and find that Elavl1cKO mice exhibit early onset eye defects namely, cataract and
microphthalmia. In this proposal, we will test the overarching hypothesis that Elavl1 mediates post-transcriptional
gene expression control over key regulators of lens development, disruption of which causes cataract and
microphthalmia. Specifically, we will address the following goals. (Aim 1) Characterize the pathogenesis of lens
defects in Elavl1cKO mice and gain insights into the structural and molecular underpinning of these defects by
comparative analysis of lens morphology, transcriptome and proteome. (Aim 2) Test the mechanism of Elavl1-
mediated control of post-transcriptional gene expression in the lens. Specifically, we will investigate the
molecular mechanism of Elavl1 function in control of the key lens development/differentiation transcription factors
Pax6, c-Maf and Prox1 among other targets. Identify direct RNA targets of Elavl1 by RNA-immunoprecipitation
followed by RNA-Sequencing. (Aim 3) Examine how Elavl1 and Celf1 coordinately mediate post-transcriptional
control in the lens and integrate and analyze all the molecular, genomic and functional data generated above to
derive Elavl1 and Celf1-regulatory networks in the lens. The expected overall impact of these innovative
investigative approaches ...

## Key facts

- **NIH application ID:** 10121802
- **Project number:** 2R01EY021505-10
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Salil Lachke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,800
- **Award type:** 2
- **Project period:** 2011-04-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121802

## Citation

> US National Institutes of Health, RePORTER application 10121802, Post transcriptional control of gene expression in the lens (2R01EY021505-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10121802. Licensed CC0.

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