Mutations in the RNA Granule Component TDRD7 Cause Cataract and Glaucoma
SCIENCE
Authors: 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.
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.
Zebrafish Staufen1 and Staufen2 are required for the survival and migration of primordial germ cells
DEVELOPMENTAL BIOLOGY
Authors: Ramasamy, S; Wang, H; Quach, HNB; Sampath, K
Abstract
in sexually reproducing organisms, primordial germ cells (PGCs) give rise to the cells of the germ line, the gametes. In many animals,. PGCS are set apart from somatic cells early during embryogenesis. Work in Drosophila, C elegans, Xenopus, and zebrafish has shown that maternally provided localized cytoplasmic determinants specify the germ line in these organisms (Raz, E., 2003. Primordial germ-cell development: the zebrafish perspective. Nat. Rev., Genet. 4, 690-700; Santos, A.C., Lehmann, R., 2004. Germ cell specification and migration in Drosophila and beyond. Curr. Biol. 14, R578-R589) The Drosophila RNA-binding, protein, Staufen is required for germ cell fort-nation, and mutations in stau result in a maternal effect grandchild-less phenotype (Schupbach, T., Wieschaus, E., 1989. Female sterile mutations on the second chromosome of Drosophila melanogaster: 1. Maternal effect mutations. Genetics 121, 101-17). Here we describe the functions of two zebrafish Staufen-related proteins, Stau1 and Stau2. When Stau1 or Stau2 functions are compromised in embryos by injecting antisense morpholino modified oligonucleotides or dominant-negative Stan peptides, germ layer patterning is not affected. However, expression of the PGC marker vasa is not maintained. Furthermore, expression of a green fluorescent protein (GFP):nanos 3'UTR fusion protein in genii cells shows that PGC migration is aberrant, and the mis-migrating PGCs do not survive in Stau-compromised embryos. Stau2 is also required for survival of neurons in the central nervous system (CNS). These phenotypes are rescued by co-injection of Drosophila stau mRNA. Thus.. staufen has an evolutionarily conserved function in germ cells. In addition, we have identified a function for Stan proteins in PGC migration. (c) 2006 Elsevier Inc. All rights reserved.