During oogenesis, numerous messenger RNAs (mRNAs) are maintained in a translationally silenced state. In eukaryotic cells, various translation inhibition and mRNA degradation mechanisms congregate in cytoplasmic processing bodies (P bodies). The P body protein Dhh1 inhibits translation and promotes decapping-mediated mRNA decay together with Pat1 in yeast, and has been implicated in mRNA storage in metazoan oocytes. Here, we have investigated in Caenorhabditis elegans whether Dhh1 and Pat1 generally function together, and how they influence mRNA sequestration during oogenesis. We show that in somatic tissues, the Dhh1 orthologue (CGH-1) forms Pat1 (patr-1)-dependent P bodies that are involved in mRNA decapping. In contrast, during oogenesis, CGH-1 forms patr-1–independent mRNA storage bodies. CGH-1 then associates with translational regulators and a specific set of maternal mRNAs, and prevents those mRNAs from being degraded. Our results identify somatic and germ cell CGH-1 functions that are distinguished by the involvement of PATR-1, and reveal that during oogenesis, numerous translationally regulated mRNAs are specifically protected by a CGH-1–dependent mechanism.
Inherited mutations of the BRCA1 gene predispose to cancer of the breast, ovaries and other organs. The BRCA1 protein product is implicated in the maintenance of chromosomal integrity as BRCA1-deficient cells display gross chromosomal rearrangements. Chromosomal instability in BRCA1-deficient cells is related to inappropriate DNA double-strand break repair. The role of the BRCA1 gene in the maintenance of chromosomal integrity is linked to a number of biological properties of its protein product including transcriptional regulation. The aim of this study is to identify genes that are regulated by BRCA1. Initial attempts to overexpress BRCA1 in breast cancer cells with the tightly-regulated ecdysone inducible system did not result in the desired levels of BRCA1 protein and ectopic BRCA1 expression was therefore performed by using the constitutive expression vector. In this study, we have identified genes whose expression levels are upregulated as a result of BRCA1 overexpression in MCF7 breast carcinoma cells by using the suppression subtractive hybridisation (SSH) method. Differential screening, sequencing and homology search studies showed that BRCA1 overexpression in breast cancer cells leads to transcriptional upregulation of distinct classes of genes encoding proteins involved in cellular processes such as DNA repair, chromosome assembly and segregation, signal transduction, RNA surveillance, ubiquitin-mediated proteolysis, amino acid transport, RNA metabolism and glucose metabolism. This study is the first to report BRCA1-
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