%0 Journal Article
%T Taking U out, with two nucleases?
%A I Saira Mian
%A Elizabeth A Worthey
%A Reza Salavati
%J BMC Bioinformatics
%D 2006
%I BioMed Central
%R 10.1186/1471-2105-7-305
%X 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.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.Most mitochondrial mRNAs in trypanosomatid parasites such as Trypanosoma, and Leishmania species undergo RNA editing [1-3]. This post-transcriptional process produces mature and functional mRNAs through a series of coordinated steps catalysed by a multi-protein complex that inserts and deletes uridylates (Us) specified by guide RNAs (gRNAs). One hypothesis posits a structural and functional subdivision of the editosome into insertion and deletion subcomplexes [4-8]. Editosome proteins with endonuclease (REN1, REN2) [9,10], terminal uridylyl transferase (TUTase; RET1, RET2) [6,11,12], 3' exouridylylase (exoUase; REX1, REX2[5,13], Ernst et al., unpublished), ligase (REL1, REL2) [5,8,14,15], and helicase (REH1) [16] activities have been identified and functionally characterized. Sets of proteins related by sequence similarity exhibit both unique and common functions. For instance, REN1 is an endoribonuclease that is specific for RNA editing deletion sites whereas REN2 is specific for RNA editing insertion sites. RET1 is implicated in the addition of the non-encoded 3'-oligo U tails to gRNAs but RET2 adds Us to pre-edited mRNAs. REL1 may be involved in
%U http://www.biomedcentral.com/1471-2105/7/305