Publication Date:
2011-03-26
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279122/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279122/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- P01 GM061354/GM/NIGMS NIH HHS/ -- P01 GM061354-07/GM/NIGMS NIH HHS/ -- R01 EY010123/EY/NEI NIH HHS/ -- R01 EY010123-15/EY/NEI NIH HHS/ -- R01 EY011721/EY/NEI NIH HHS/ -- R01 EY011721-15/EY/NEI NIH HHS/ -- R01 EY10123/EY/NEI NIH HHS/ -- R01 EY11721/EY/NEI NIH HHS/ -- R01 HD060050/HD/NICHD NIH HHS/ -- R01 HD060050-04/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1571-6. doi: 10.1126/science.1195970.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436445" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cataract/congenital/*genetics/pathology
;
Cell Line
;
Chick Embryo
;
Crystallins/genetics/metabolism
;
Cytoplasmic Granules/metabolism
;
Embryonic Development
;
Female
;
*Gene Expression Regulation, Developmental
;
Gene Knockdown Techniques
;
Glaucoma/*genetics
;
Humans
;
Hypospadias/genetics
;
Lens, Crystalline/embryology/*metabolism
;
Male
;
Mice
;
Mutation
;
Organogenesis
;
Protein Biosynthesis
;
RNA, Messenger/*genetics/*metabolism
;
RNA-Binding Proteins/genetics/metabolism
;
Ribonucleoproteins/genetics/*metabolism
;
Spermatogenesis/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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