Comparative genomics and protein domain graph analyses link ubliquitination and RNA metabolism

The human gene parkin, known to cause familial Parkinson disease, as well as several other genes, likely involved in other neurode-generative diseases or in cancer, encode proteins of the RBR family of ubiquitin ligases. Here, vie describe the structural diversity of the RBR family in order to infer their functional roles. Of particular interest is a relationship detected between RBR-mediated ubiquitination and RNA metabolism: a few RBR, proteins contain RNA binding domains and DEAH-box RNA helicase domains. Global protein domain graph analyses demonstrate that this connection is not RBR-specific, but instead many other proteins contain both ubiquitination and RNA-related domains. These proteins are present in animals, plants and fungi, suggesting that the link between these two cellular processes is ancient. Our results show that global bioinformatic approaches, involving comparative genomics and domain network analyses, may unearth novel functional relationships involving well-known and thoroughly studied groups of proteins. (c) 2005 Elsevier Ltd. All rights reserved.