Comparative genomic analysis reveals a novel mitochondrial isoform of human rTS protein and unusual phylogenetic distribution of the rTS gene
| Autor: | Jayakumar R Nair, John J. McGuire, Ping Liang, Bruce J. Dolnick, Lei Song |
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| Rok vydání: | 2005 |
| Předmět: |
Gene isoform
lcsh:QH426-470 Sequence analysis lcsh:Biotechnology Blotting Western Molecular Sequence Data Biology Models Biological behavioral disciplines and activities Genome Cell Line 03 medical and health sciences Protein structure Start codon lcsh:TP248.13-248.65 Genetics Animals Humans Protein Isoforms Amino Acid Sequence Codon Peptide sequence Gene Phylogeny 030304 developmental biology 0303 health sciences Base Sequence 030302 biochemistry & molecular biology Computational Biology Genomics Thymidylate Synthase Mitochondria Protein Structure Tertiary lcsh:Genetics Horizontal gene transfer Research Article Subcellular Fractions Biotechnology |
| Zdroj: | BMC Genomics, Vol 6, Iss 1, p 125 (2005) BMC Genomics |
| ISSN: | 1471-2164 |
| DOI: | 10.1186/1471-2164-6-125 |
| Popis: | Background The rTS gene (ENOSF1), first identified in Homo sapiens as a gene complementary to the thymidylate synthase (TYMS) mRNA, is known to encode two protein isoforms, rTSα and rTSβ. The rTSβ isoform appears to be an enzyme responsible for the synthesis of signaling molecules involved in the down-regulation of thymidylate synthase, but the exact cellular functions of rTS genes are largely unknown. Results Through comparative genomic sequence analysis, we predicted the existence of a novel protein isoform, rTS, which has a 27 residue longer N-terminus by virtue of utilizing an alternative start codon located upstream of the start codon in rTSβ. We observed that a similar extended N-terminus could be predicted in all rTS genes for which genomic sequences are available and the extended regions are conserved from bacteria to human. Therefore, we reasoned that the protein with the extended N-terminus might represent an ancestral form of the rTS protein. Sequence analysis strongly predicts a mitochondrial signal sequence in the extended N-terminal of human rTSγ, which is absent in rTSβ. We confirmed the existence of rTS in human mitochondria experimentally by demonstrating the presence of both rTSγ and rTSβ proteins in mitochondria isolated by subcellular fractionation. In addition, our comprehensive analysis of rTS orthologous sequences reveals an unusual phylogenetic distribution of this gene, which suggests the occurrence of one or more horizontal gene transfer events. Conclusion The presence of two rTS isoforms in mitochondria suggests that the rTS signaling pathway may be active within mitochondria. Our report also presents an example of identifying novel protein isoforms and for improving gene annotation through comparative genomic analysis. |
| Databáze: | OpenAIRE |
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