Mutations in the RNA granule component TDRD7 cause cataract and glaucoma

Salil A Lachke; 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

doi:10.1126/science.1195970

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Mutations in the RNA granule component TDRD7 cause cataract and glaucoma

Journal article

Peer reviewed

Mutations in the RNA granule component TDRD7 cause cataract and glaucoma

Salil A Lachke, Fowzan S Alkuraya, Stephen C Kneeland, Takbum Ohn, Anton Aboukhalil, Gareth R Howell, Irfan Saadi, Resy Cavallesco, Yingzi Yue, Anne C-H Tsai, …

Science (American Association for the Advancement of Science), Vol.331(6024), pp.1571-1576

03/25/2011

DOI: 10.1126/science.1195970

PMCID: PMC3279122

PMID: 21436445

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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.

Mutation

Crystallins - metabolism

RNA-Binding Proteins - genetics

Protein Biosynthesis

Spermatogenesis - genetics

Humans

Cataract - pathology

Male

RNA, Messenger - metabolism

Gene Knockdown Techniques

Gene Expression Regulation, Developmental

Cytoplasmic Granules - metabolism

Female

Ribonucleoproteins - genetics

Cell Line

Lens, Crystalline - embryology

RNA, Messenger - genetics

Lens, Crystalline - metabolism

Hypospadias - genetics

Crystallins - genetics

Ribonucleoproteins - metabolism

Embryonic Development

Chick Embryo

Organogenesis

Animals

Cataract - congenital

Cataract - genetics

Mice

Glaucoma - genetics

RNA-Binding Proteins - metabolism

Details

Title: Subtitle: Mutations in the RNA granule component TDRD7 cause cataract and glaucoma
Creators: Salil A Lachke - Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
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
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.331(6024), pp.1571-1576
DOI: 10.1126/science.1195970
PMID: 21436445
PMCID: PMC3279122
NLM abbreviation: Science
ISSN: 1095-9203
eISSN: 1095-9203
Publisher: United States
Grant note: R01 EY011721 / NEI NIH HHS R01 EY11721 / NEI NIH HHS P01 GM061354 / NIGMS NIH HHS P01 GM061354-07 / NIGMS NIH HHS R01 EY010123-15 / NEI NIH HHS R01 HD060050 / NICHD NIH HHS R01 EY10123 / NEI NIH HHS Howard Hughes Medical Institute R01 EY010123 / NEI NIH HHS R01 EY011721-15 / NEI NIH HHS R01 HD060050-04 / NICHD NIH HHS
Language: English
Date published: 03/25/2011
Academic Unit: Stead Family Department of Pediatrics; Ophthalmology and Visual Sciences
Record Identifier: 9983979942102771

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