RNA-binding proteins play critical roles in various aspects of cell function, such as splicing, transcription termination and mRNA storage. They are similarly essential for viruses whose replication strategies involve RNA intermediates. In a search for proteins that bind to hepatitis B virus (HBV) RNAs, Stefan Kreft and Michael Nassal have identified a human RNA-binding protein, hRUL138, that looks like nothing yet seen (see p. 605). hRUL138 is a 138 kDa cytoplasmic protein that is expressed in most tissues and could be associated with the ER. It contains a novel RNA-binding domain in which the only recognizable motif is a coiled-coil region. Remarkably, hRUL138 also contains the RING-H2 signature characteristic of certain ubiquitin ligases (E3 enzymes). Indeed, Kreft and Nassal show that this has self- and trans-ubiquitin-ligase activity in vitro and can drive proteasome-mediated degradation of hRUL138 in vivo. The cellular target RNA for hRUL138 is not yet clear; however, the unusual combination of RNA-binding and ubiquitin ligase activities in one protein raises some interesting possibilities. Other RNA-binding proteins or RNPs, for example, could be targets of the hRUL138 ubiquitin ligase, and it might use RNAs to increase target specificity.
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