Analysis Of Human Disease Susceptibility Gene ELAC2 And DJ-1 Biological Information Eukaryotes

ELAC2is the candidate prostate cancer susceptibility gene, tRNase Z removes the3’-trailer sequences from precursor tRNAs, which is an essential step preceding the addition of the CCA sequence. Based on the sequence sizes,they exist two forms:the short tRNase Z (tRNase Zs) and long tRNase Z (tRNase ZL);based on the sequence characteristics, they can be divided into two major types:bacterial-type tRNase Zs and eukaryotic-type tRNase ZL, and one minor type, Thermotoga maritima (TM)-type tRNase Zs.To further investigate the evolutionary diversity of tRNase Z, we mined the green plant and metazoan genome sequences for tRNase Z. We report the identification and analysis of candidate tRNase Zs in them, and found some interesting results. It appears that green plants contain multiple distinct tRNase Zs predicted to reside in different subcellular compaitments,like Arabidopsis thaliana exists4tRNase Zs, Setaria italica has5tRNase Zs. Furthermore, while the bacterial-type tRNase Zss are present only in basal land plants and green algae, the TM-type tRNase Zss are widespread in green plants. The protein sequences of the TM-type tRNase Zss identified in green plants are similar to those of the bacterial-type tRNase Zss but have distinct features, including the TM-type flexible arm, the variant catalytic HEAT and HST motifs, and a lack of the PxKxRN motif. Examination of flowering plant chloroplast tRNA genes reveals that many of these genes encode partial CCA sequences. Based on our results and previous studies, we predict that the plant TM-type tRNase Zss may not recognize the CCA sequence as an anti-determinant. We also surveyed the metazoan genome sequences for tRNase Z and found that the majority of deuterostomes, lophotrochozoans and nonbilaterian lower metazoans analyzed have one tRNase Zs and one tRNase ZL genes, whereas nematodes and arthropods possess only a single tRNase ZL gene. It appears that in metazoans, a single nuclear tRNase ZL gene encodes both the nuclear and mitochondrial forms of tRNA3’-end processing enzyme through mechanisms that include alternative translation initiation from two in-frame start codons and alternative splicing. We also found a previously unappreciated motif, AxDx, present in the C-terminal region of both tRNase Zss and tRNase ZLs. The AxDx motif consisting mainly of a very short loop is potentially close enough to form hydrogen bonds with the loop containing the PxKxRN or PxPxRG motif. Through complementation analysis, we demonstrated the likely functional importance of the AxDx motif. Our findings substantially expand the current repertoire of the TM-type tRNase Zss and hint at the possibility that these proteins may have been selected for their ability to process chloroplast pre-tRNAs with whole or partial CCA sequences. Our results suggest that in metazoans a single tRNase ZL has evolved to participate in both nuclear and mitochondrial tRNA3’-end processing, whereas tRNase Zs may have evolved new functions.DJ-1, a cancer-and Parkinson’s disease (PD)-associated protein, protects cells from toxic stresses. DJ-1and Hsp31proteins belong to two different subfamilies of the DJ-1superfamily, including the Parkinson’s disease-associated DJ-1protein (HsDJ-1) and the Escherichia coli heat shock protein Hsp31(EcHsp31), and are the most likely candidates for GLO3.Methylglyoxal (MG), known as reactive carbonyl species, is a toxic metabolite synthesized in living systems primarily as a byproduct of glycolysis. Mechanisms of MG detoxicification include the glutathione (GSH)-dependent pathway consisting of glyoxalase I (GLO1) and glyoxalase II (GLO2), and GSH-independent pathway catalyzed by glyoxalase Ⅲ (GLO3). We performed a systematic survey of homologs of these proteins in fungi. DJ-1proteins have a very limited distribution in fungi, whereas Hsp31proteins are widely distributed among different fungal groups.Both Schizosaccharomyces pombe DJ-1(SpDJ-1) and Saccharomyces cerevisiae Hsp31(ScHsp31) have GLO3activity in vitro. This glyoxalase activity requires a predicted catalytic triad (Glu16-Cys111-His130in SpDJ-1,Glu30-Cysl38-His139in ScHsp31).Our results suggest that fungal DJ-1and Hsp31proteins encode GLO3, which may play a role in protecting cells from MG toxicity in stationary phase. Our results also support the view that GL03activity likely evolved through convergent evolution.