Abstract
BackgroundCCCH type zinc finger proteins are RNA binding proteins with regulatory functions at all stages of mRNA metabolism. The best-characterized member, tritetraproline (TTP), binds to AU rich elements in 3' UTRs of unstable mRNAs, mediating their degradation. In kinetoplastids, CCCH type zinc finger proteins have been identified as being involved in the regulation of the life cycle and possibly the cell cycle. To date, no systematic listing of CCCH proteins in kinetoplastids is available.ResultsWe have identified the complete set of CCCH type zinc finger proteins in the available genomes of the kinetoplastid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major. One fifths (20%) of all CCCH motifs fall into non-conventional classes and many had not been previously identified. One third of all CCCH proteins have more than one CCCH motif, suggesting multivalent RNA binding. One third have additional recognizable domains. The vast majority are unique to Kinetoplastida or to a subgroup within. Two exceptions are of interest: the putative orthologue of the mRNA nuclear export factor Mex67 and a 3'-5' exoribonuclease restricted to Leishmania species. CCCH motifs are absent from these proteins in other organisms and might be unique, novel features of the Kinetoplastida homologues. Of the others, several have a predicted, and in one case experimentally confirmed, connection to the ubiquitination pathways, for instance a HECT-type E3 ubiquitin ligase. The total number of kinetoplastid CCCH proteins is similar to the number in higher eukaryotes but lower than in yeast. A comparison of the genomic loci between the Trypanosomatidae homologues provides insight into both the evolution of the CCCH proteins as well as the CCCH motifs.ConclusionThis study provides the first systematic listing of the Kinetoplastida CCCH proteins. The number of CCCH proteins with more then one CCCH motif is larger than previously estimated, due to the identification of non-conventional CCCH motifs. Experimental approaches are now necessary to examine the functions of the many unique CCCH proteins as well as the function of the putative Mex67 and the Leishmania 3'-5' exoribonuclease.
Highlights
CCCH type zinc finger proteins are RNA binding proteins with regulatory functions at all stages of mRNA metabolism
The CCCH motifs belonged to all possible classes, but there was a clear enrichment in the two conventional CCCH motifs
As expected for CCCH motifs that are recognized by Pfam, the logo was similar to the Pfam sequence logo for CCCH motifs or the logos for rice and Arabidopsis CCCH proteins [16]
Summary
CCCH type zinc finger proteins are RNA binding proteins with regulatory functions at all stages of mRNA metabolism. No systematic listing of CCCH proteins in kinetoplastids is available Pathogenic kinetoplastid protozoa, such as the widely studied 'Tritryps' Trypanosoma cruzi (Tc), Leishmania major (Lm) and Trypanosoma brucei (Tb), have complex biphasic life cycles and require changes in gene expression in response to extrinsic and intrinsic signals. At least 5% of all Tb genes are developmentally regulated at the mRNA level between any two of the experimentally tractable life cycle stages [1,2,3,4]. CCCH proteins have between 1 and 6 CCCH motifs These were originally defined as C-X6-14-C-X4-5-C-X3-H [15] but recently redefined as C-X4-15-C-X4-6-C-X3-H, following the genome wide analysis of the rice and Arabidopsis CCCH proteins [16]
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