SECIS binding proteins

Abstract

The 3′-untranslated regions (UTRs) of selenoprotein mRNAs contain a stable stem-loop termed the selenocysteine insertion sequence (SECIS) element. Among the trans-acting factors that are thought to be required for selenocysteine (Sec) insertion are RNA binding proteins that interact with the SECIS element. In addition to several proteins which bind non-specifically, this element is specifically bound by SECIS binding protein 2 (SBP2), and this interaction is required for Sec insertion. SBP2 is a novel 94 kDa protein that contains an RNA binding domain found in ribosomal proteins and eukaryotic translation termination release factor 1 (eRF-1). SBP2 specifically interacts with the conserved AUGA element in the SECIS element core, but binding is not affected by mutations to the conserved AAA motif. Mutation analysis of SBP2 mutants indicates that it has distinct functional and RNA binding domains. While the mechanism of SBP2 action remains to be determined, we have recently observed that it is stably associated with ribosomes in vivo and in vitro, and that this association requires both the RNA binding and functional domains. These recent data suggest that SBP2 may be involved in defining a subset of ribosomes capable of translating selenoprotein mRNAs.