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Evolutionary analysis of WD40 super family proteins involved in spindle checkpoint and RNA export: molecular evolution of spindle checkpoint.

ABSTRACT: The spindle checkpoint delays sister chromatid separation until all chromosomes have undergone bipolar spindle attachment. Previous studies have revealed BUB3, as an essential spindle checkpoint protein and its extensive sequence similarity with Rae1 (Gle2), a highly conserved member of WD40 repeat protein family throughout their length which was first shown to be involved in mRNA export. However, the recent discovery of Rae1 as an essential mitotic checkpoint protein, based on the studies from mouse and drosophila, has renewed the interest in its function during cell division. Study of evolution of proteins involved in checkpoint might throw light on evolution of eukaryotic cell cycle regulation. Here we report the evolutionary relationships between these two WD40 repeat family proteins. Amino acid sequences of BUB3 and Rae1 homologs were retrieved from various databases and phylogenetic analysis was performed with the MEGA program. Multiple sequence alignments of these two protein homologues with the ClustalX software revealed specific amino acid signatures corresponding to the protein function and also few amino acids, which are conserved in BUB3 and Rae1 indicating some common overlapping function. Data indicated a common ancestral origin of these two important proteins and further suggest that, BUB3 mediated cell cycle checkpoint might have evolved with compartmentalization of genetic material into the nucleus in eukaryotes.

SUBMITTER: Reddy DM

PROVIDER: S-EPMC2561167 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Evolutionary analysis of WD40 super family proteins involved in spindle checkpoint and RNA export: molecular evolution of spindle checkpoint.

Reddy Duvvuru Muni Rajasekhara DM Aspatwar Ashok A Dholakia Bhushan Bhalchandra BB Gupta Vidya Shrikant VS

Bioinformation 20080801 10

The spindle checkpoint delays sister chromatid separation until all chromosomes have undergone bipolar spindle attachment. Previous studies have revealed BUB3, as an essential spindle checkpoint protein and its extensive sequence similarity with Rae1 (Gle2), a highly conserved member of WD40 repeat protein family throughout their length which was first shown to be involved in mRNA export. However, the recent discovery of Rae1 as an essential mitotic checkpoint protein, based on the studies from ...[more]

PMID: 18841243

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Project description:BackgroundThe establishment of the nuclear membrane resulted in the physical separation of transcription and translation, and presented early eukaryotes with a formidable challenge: how to shuttle RNA from the nucleus to the locus of protein synthesis. In prokaryotes, mRNA is translated as it is being synthesized, whereas in eukaryotes mRNA is synthesized and processed in the nucleus, and it is then exported to the cytoplasm. In metazoa and fungi, the different RNA species are exported from the nucleus by specialized pathways. For example, tRNA is exported by exportin-t in a RanGTP-dependent fashion. By contrast, mRNAs are associated to ribonucleoproteins (RNPs) and exported by an essential shuttling complex (TAP-p15 in human, Mex67-mtr2 in yeast) that transports them through the nuclear pore. The different RNA export pathways appear to be well conserved among members of Opisthokonta, the eukaryotic supergroup that includes Fungi and Metazoa. However, it is not known whether RNA export in the other eukaryotic supergroups follows the same export routes as in opisthokonts.MethodsOur objective was to reconstruct the evolutionary history of the different RNA export pathways across eukaryotes. To do so, we screened an array of eukaryotic genomes for the presence of homologs of the proteins involved in RNA export in Metazoa and Fungi, using human and yeast proteins as queries.ResultsOur genomic comparisons indicate that the basic components of the RanGTP-dependent RNA pathways are conserved across eukaryotes, and thus we infer that these are traceable to the last eukaryotic common ancestor (LECA). On the other hand, several of the proteins involved in RanGTP-independent mRNA export pathways are less conserved, which would suggest that they represent innovations that appeared later in the evolution of eukaryotes.ConclusionsOur analyses suggest that the LECA possessed the basic components of the different RNA export mechanisms found today in opisthokonts, and that these mechanisms became more specialized throughout eukaryotic evolution.

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Evolutionary analysis of WD40 super family proteins involved in spindle checkpoint and RNA export: molecular evolution of spindle checkpoint.

Publications

Evolutionary analysis of WD40 super family proteins involved in spindle checkpoint and RNA export: molecular evolution of spindle checkpoint.

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