2. Academic Validation
  3. Mutations in the RNA granule component TDRD7 cause cataract and glaucoma

Mutations in the RNA granule component TDRD7 cause cataract and glaucoma

  • Science. 2011 Mar 25;331(6024):1571-6. doi: 10.1126/science.1195970.
Salil A Lachke 1,  Fowzan S Alkuraya,  Stephen C Kneeland,  Takbum Ohn,  Anton Aboukhalil,  Gareth R Howell,  Irfan Saadi,  Resy Cavallesco,  Yingzi Yue,  Anne C-H Tsai,  K Saidas Nair,  Mihai I Cosma,  Richard S Smith,  Emily Hodges,  Suad M Alfadhli,  Amal Al-Hajeri,  Hanan E Shamseldin,  Abdulmutalib Behbehani,  Gregory J Hannon,  Martha L Bulyk,  Arlene V Drack,  Paul J Anderson,  Simon W M John,  Richard L Maas
Affiliations

Affiliation

  • 1 Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
PMID: 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.

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