Dicer promotes genome stability via the bromodomain transcriptional co-activator BRD4.

RNA interference is required for post-transcriptional silencing, but also has additional roles in transcriptional silencing of centromeres and genome stability. However, these roles have been controversial in mammals. Strikingly, we found that Dicer-deficient embryonic stem cells have strong proliferation and chromosome segregation defects as well as increased transcription of centromeric satellite repeats, which triggers the interferon response. We conducted a CRISPR-Cas9 genetic screen to restore viability and identified transcriptional activators, histone H3K9 methyltransferases, and chromosome segregation factors as suppressors, resembling Dicer suppressors identified in independent screens in fission yeast. The strongest suppressors were mutations in the transcriptional co-activator Brd4, which reversed the strand-specific transcription of major satellite repeats suppressing the interferon response, and in the histone acetyltransferase Elp3. We show that identical mutations in the second bromodomain of Brd4 rescue Dicer-dependent silencing and chromosome segregation defects in both mammalian cells and fission yeast. This remarkable conservation demonstrates that RNA interference has an ancient role in transcriptional silencing and in particular of satellite repeats, which is essential for cell cycle progression and proper chromosome segregation. Our results have pharmacological implications for cancer and autoimmune diseases characterized by unregulated transcription of satellite repeats.

Use of nanosilver in consumer products.

Silver nanoparticles (AgNP; many other names such as nanosilver and colloidal silver) have already been used in everyday consumer products requiring broad spectrum antibiotic performance because of their enormous surface area and reactivity. Faunce and Watal [1] recently have critically analyzed the international regulatory issues for medical and domestic use in USA, EU, UK, and Australia. They found that in spite of the fact numerous studies have been made in the past decades, but many scientists are still uncertain of its safety. Very recently, Powers mentioned in her dissertation that her results showed positive that Ag+ and AgNP are developmental neurotoxicants in vitro and in vivo [2]. Therefore, there is a need to conduct a study to identify a global landscape of AgNPs and their products, and their manufacturers. A market- based intellectual property (IP) study has been conducted to examine the current global patent landscape of companies using AgNP in their consumer product development and production from 1980 to 2010. Detailed information in the compositions and formulations is extracted using a "two-stage" stage-gate process from the IP activity in the use of nanosilver. The first stage is in commercial products and the second stage is in consumer products. In the first stage for AgNP and AgNP-based commercial products, there were 7,422 patent families from January 1, 1980 to December 31, 2010. In the second stage for AgNP-based consumer products, 932 patent families from January 1, 1980 to December 31, 2010 were found. Korea, China and USA were found to be the major players in AgNP and AgNP-based commercial and consumer products. However, the recent patenting downturn was observed probably due to rising price in silver metal, regulatory uncertainty, public perception, and health safety & environmental (HS&E) issues.