Key result
RNAi-mediated down-regulation of ADAR1 in HeLa cells resulted in the up-regulation of several genes that undergo A-to-I editing and are regulated by hUpf1.
The study reveals a novel interaction between ADAR1 and hUpf1 in the nucleus, suggesting a coordinated regulatory pathway involving A-to-I RNA editing and RNA degradation.
Does not yet inform clinical practice; leaves open the therapeutic relevance of ADAR1-hUpf1 interactions in human disease.
Posttranscriptional regulation is an important step in the regulation of gene expression. In this article, we show an unexpected connection between two proteins that participate in different processes of posttranscriptional regulation that ensures the production of functional mRNA molecules. Specifically, we show that the A-to-I RNA editing protein adenosine deaminase that acts on RNA 1 (ADAR1) and the human Upf1 (hUpf1) protein involved in RNA surveillance are found associated within nuclear RNA-splicing complexes. A potential functional role for this association was revealed by RNAi-mediated down-regulation of ADAR1, which was accompanied by up-regulation of a number of genes previously shown to undergo A-to-I editing in Alu repeats and to be down-regulated by hUpf1. This study suggests a regulatory pathway by a combination of ADAR1 A-to-I editing enzyme and RNA degradation presumably with the aid of hUpf1.
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Agranat et al. (2008) studied this question. RNAi of ADAR1 vs. Untreated cells or siRNA against firefly luciferase was evaluated on Up-regulation of genes edited by ADARs and regulated by hUpf1 (e.g., PISD, MGC10471, DAP3, SARS). RNAi-mediated down-regulation of ADAR1 in HeLa cells resulted in the up-regulation of several genes that undergo A-to-I editing and are regulated by hUpf1.
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