title: Mutations in the RNA granule component TDRD7 cause cataract and glaucoma.
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.
authors: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors: Salil A
authors: SA
authors: Lachke
authors: Fowzan S
authors: FS
authors: Alkuraya
authors: Stephen C
authors: SC
authors: Kneeland
authors: Takbum
authors: T
authors: Ohn
authors: Anton
authors: A
authors: Aboukhalil
authors: Gareth R
authors: GR
authors: Howell
authors: Irfan
authors: I
authors: Saadi
authors: Resy
authors: R
authors: Cavallesco
authors: Yingzi
authors: Y
authors: Yue
authors: Anne C-H
authors: AC
authors: Tsai
authors: K Saidas
authors: KS
authors: Nair
authors: Mihai I
authors: MI
authors: Cosma
authors: Richard S
authors: RS
authors: Smith
authors: Emily
authors: E
authors: Hodges
authors: Suad M
authors: SM
authors: Alfadhli
authors: Amal
authors: A
authors: Al-Hajeri
authors: Hanan E
authors: HE
authors: Shamseldin
authors: Abdulmutalib
authors: A
authors: Behbehani
authors: Gregory J
authors: GJ
authors: Hannon
authors: Martha L
authors: ML
authors: Bulyk
authors: Arlene V
authors: AV
authors: Drack
authors: Paul J
authors: PJ
authors: Anderson
authors: Simon W M
authors: SW
authors: John
authors: Richard L
authors: RL
authors: Maas
mesh_terms: D000818:Animals; D002386:Cataract / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D002460:Cell Line; D002642:Chick Embryo; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D005901:Glaucoma / Q000235:genetics*; D006801:Humans; D007021:Hypospadias / Q000235:genetics; D007908:Lens, Crystalline / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009154:Mutation; D038081:Organogenesis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D003459:Crystallins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C492187:Stau1 protein, mouse; C517522:TDRD7 protein, mouse; C557201:Tdrd7 protein, human