Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma

Lachke, S. A., Alkuraya, F. S., Kneeland, S. C., Ohn, T., Aboukhalil, A., Howell, G. R., Saadi, I., Cavallesco, R., Yue, Y. Z., Tsai, A. C. H., Nair, K. S., Cosma, M. I., Smith, R. S., Hodges, E., AlFadhli, S. M., Al-Hajeri, A., Shamseldin, H. E., Behbehani, A., Hannon, G. J., Bulyk, M. L., Drack, A. V., Anderson, P. J., John, S. W. M., Maas, R. L. (March 2011) Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma. Science, 331 (6024). pp. 1571-1576. ISSN 0036-8075

URL: https://www.ncbi.nlm.nih.gov/pubmed/21436445
DOI: 10.1126/science.1195970

Abstract

The precise transcriptional regulation of gene expression is essential for vertebrate development, but the role of posttranscriptional regulatory mechanisms is less clear. Cytoplasmic RNA granules (RGs) function in the posttranscriptional control of gene expression, but the extent of RG involvement in organogenesis is unknown. We describe two human cases of pediatric cataract with loss-of-function mutations in TDRD7 and demonstrate that Tdrd7 nullizygosity in mouse causes cataracts, as well as glaucoma and an arrest in spermatogenesis. TDRD7 is a Tudor domain RNA binding protein that is expressed in lens fiber cells in distinct TDRD7-RGs that interact with STAU1-ribonucleoproteins (RNPs). TDRD7 coimmunoprecipitates with specific lens messenger RNAs (mRNAs) and is required for the posttranscriptional control of mRNAs that are critical to normal lens development and to RG function. These findings demonstrate a role for RGs in vertebrate organogenesis.

Item Type: Paper
Uncontrolled Keywords: cytoplasmic processing bodies mammalian stress granules eukaryotic messenger rnas male germ cells p bodies chromatoid body translation proteins decay localization
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > post transcriptional modification
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Editor Margaret Fantz
Date: 25 March 2011
Date Deposited: 17 Apr 2012 19:50
Last Modified: 02 Dec 2016 17:38
PMCID: PMC3279122
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26112

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