Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Science. 2011 Mar 25;331(6024):1571-6. 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.
精确的基因表达转录调控对于脊椎动物的发育至关重要，但转录后调控机制的作用尚不清楚。细胞质 RNA 颗粒 (RGs) 在基因表达的转录后调控中发挥作用，但 RG 在器官发生中的参与程度尚不清楚。我们描述了两例儿童白内障病例，这些病例的 TDRD7 存在功能丧失突变，并证明小鼠的 Tdrd7 纯合缺失会导致白内障、青光眼和精子发生停滞。TDRD7 是一种含有 Tudor 结构域的 RNA 结合蛋白，在晶状体纤维细胞中表达，存在与 STAU1-核糖核蛋白（RNP）相互作用的特定 TDRD7-RG。TDRD7 与特定的晶状体信使 RNA (mRNA) 共免疫沉淀，并且对于对正常晶状体发育和 RG 功能至关重要的 mRNA 的转录后调控是必需的。这些发现表明 RG 在脊椎动物器官发生中起作用。
