Research article

Taking U out, with two nucleases?

I Saira Mian¹ , Elizabeth A Worthey and Reza Salavati^2,3

¹  Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720-8265, USA

²  Seattle Biomedical Research Institute, Seattle, Washington, 98109, USA

³  McGill University, Institute of Parasitology, Ste.-Anne-De-Bellevue, Quebec, H9X 3V9, Canada

author email corresponding author email

BMC Bioinformatics 2006, 7:305doi:10.1186/1471-2105-7-305

Published:	16 June 2006

Abstract

Background

REX1 and REX2 are protein components of the RNA editing complex (the editosome) and function as exouridylylases. The exact roles of REX1 and REX2 in the editosome are unclear and the consequences of the presence of two related proteins are not fully understood. Here, a variety of computational studies were performed to enhance understanding of the structure and function of REX proteins in Trypanosoma and Leishmania species.

Results

Sequence analysis and homology modeling of the Endonuclease/Exonuclease/Phosphatase (EEP) domain at the C-terminus of REX1 and REX2 highlights a common active site shared by all EEP domains. Phylogenetic analysis indicates that REX proteins contain a distinct subfamily of EEP domains. Inspection of three-dimensional models of the EEP domain in Trypanosoma brucei REX1 and REX2, and Leishmania major REX1 suggests variations of previously characterized key residues likely to be important in catalysis and determining substrate specificity.

Conclusion

We have identified features of the REX EEP domain that distinguish it from other family members and hence subfamily specific determinants of catalysis and substrate binding. The results provide specific guidance for experimental investigations about the role(s) of REX proteins in RNA editing.