April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Sequences in the Rhodopsin 3’ UTR Bind IMPDH with High Affinity
Author Affiliations & Notes
  • Dharia A. McGrew
    Molecular & Cell Biology, Brandeis University, Waltham, Massachusetts
  • Lizbeth Hedstrom
    Molecular & Cell Biology, Brandeis University, Waltham, Massachusetts
  • Footnotes
    Commercial Relationships  Dharia A. McGrew, None; Lizbeth Hedstrom, None
  • Footnotes
    Support  EY017325
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6671. doi:
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      Dharia A. McGrew, Lizbeth Hedstrom; Sequences in the Rhodopsin 3’ UTR Bind IMPDH with High Affinity. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6671.

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

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Purpose: : Mutations in the inosine monophosphate dehydrogenase type I (IMPDH1) gene cause one form of Retinitis Pigmentosa. Although IMPDH is ubiquitously expressed, the pathogenic mechanism limiting cell death to the rod photoreceptors is unknown. This study seeks to identify a tissue-specific function of IMPDH that can account for visual disease. A specific association between IMPDH1 and polyribosomes translating rhodopsin was previously shown. IMPDH1 binds nucleic acid, so we hypothesized that rhodopsin mRNA may contain a specific binding sequence that is recognized by a retina-specific splice variant of IMPDH1.

Methods: : The association of IMPDH(546) and 200 nt fragments of the 5’ and 3’ untranslated regions (UTR) of rhodopsin mRNA was probed in a filter binding assay.

Results: : We have identified a sequence within the rhodopsin 3’UTR that binds the retinal splice variant of IMPDH with high affinity. This region of 215 nt has 40 fold higher affinity than other sequences within the rhodopsin UTR.

Conclusions: : Since any perturbation of rhodopsin biosynthesis triggers apoptosis in photoreceptor cells, association of IMPDH protein with rhodopsin mRNA suggests a likely pathogenic mechanism for IMPDH1-mediated adRP. Identification of a specific sequence in the Rho message bound by IMPDH would help identify the role of IMPDH splice variants in the retina.

Keywords: retinal degenerations: cell biology • protein structure/function • mutations 

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