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; Abdul Mutalib 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

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, Abdul Mutalib Behbehani, Gregory J. Hannon, Martha L. BulykArlene V. Drack, Paul J. Anderson, Simon W.M. John, Richard L. Maas

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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.

Original language	English (US)
Pages (from-to)	1571-1576
Number of pages	6
Journal	Science
Volume	331
Issue number	6024
DOIs	https://doi.org/10.1126/science.1195970
State	Published - Mar 25 2011
Externally published	Yes

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Lachke, S. A., Alkuraya, F. S., Kneeland, S. C., Ohn, T., Aboukhalil, A., Howell, G. R., Saadi, I., Cavallesco, R., Yue, Y., Tsai, A. C. H., Nair, K. S., Cosma, M. I., Smith, R. S., Hodges, E., AlFadhli, S. M., Al-Hajeri, A., Shamseldin, H. E., Behbehani, A. M., Hannon, G. J., ... Maas, R. L. (2011). Mutations in the RNA granule component TDRD7 cause cataract and glaucoma. Science, 331(6024), 1571-1576. https://doi.org/10.1126/science.1195970

Lachke, SA, Alkuraya, FS, Kneeland, SC, Ohn, T, Aboukhalil, A, Howell, GR, Saadi, I, Cavallesco, R, Yue, Y, Tsai, ACH, Nair, KS, Cosma, MI, Smith, RS, Hodges, E, AlFadhli, SM, Al-Hajeri, A, Shamseldin, HE, Behbehani, AM, Hannon, GJ, Bulyk, ML, Drack, AV, Anderson, PJ, John, SWM & Maas, RL 2011, 'Mutations in the RNA granule component TDRD7 cause cataract and glaucoma', Science, vol. 331, no. 6024, pp. 1571-1576. https://doi.org/10.1126/science.1195970

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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.",

author = "Lachke, {Salil A.} and Alkuraya, {Fowzan S.} and Kneeland, {Stephen C.} and Takbum Ohn and Anton Aboukhalil and Howell, {Gareth R.} and Irfan Saadi and Resy Cavallesco and Yingzi Yue and Tsai, {Anne C.H.} and Nair, {K. Saidas} and Cosma, {Mihai I.} and Smith, {Richard S.} and Emily Hodges and AlFadhli, {Suad M.} and Amal Al-Hajeri and Shamseldin, {Hanan E.} and Behbehani, {Abdul Mutalib} and Hannon, {Gregory J.} and Bulyk, {Martha L.} and Drack, {Arlene V.} and Anderson, {Paul J.} and John, {Simon W.M.} and Maas, {Richard L.}",

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AU - Lachke, Salil A.

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AU - Hodges, Emily

AU - AlFadhli, Suad M.

AU - Al-Hajeri, Amal

AU - Shamseldin, Hanan E.

AU - Behbehani, Abdul Mutalib

AU - Hannon, Gregory J.

AU - Bulyk, Martha L.

AU - Drack, Arlene V.

AU - Anderson, Paul J.

AU - John, Simon W.M.

AU - Maas, Richard L.

PY - 2011/3/25

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Mutations in the RNA granule component TDRD7 cause cataract and glaucoma

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