Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma

作者：Lachke Salil A; Alkuraya Fowzan S; Kneeland Stephen C; Ohn Takbum; Aboukhalil Anton; Howell Gareth R; Saadi Irfan; Cavallesco Resy; Yue Yingzi; Tsai Anne C H; Nair K Saidas; Cosma Mihai I; Smith Richard S; Hodges Emily; AlFadhli Suad M; Al Hajeri Amal; Shamseldin Hanan E; Behbehani AbdulMutalib; Hannon Gregory J; Bulyk Martha L; Drack Arlene V; Anderson Paul J; John Simon W M^*; Maas Richard L

来源：Science, 2011, 331(6024): 1571-1576.

DOI：10.1126/science.1195970

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.

• 出版日期2011-3-25