Molecular Analysis ofMETTL1,a Novel Human Methyltransferase-like Gene with a High Degree of Phylogenetic Conservation

A novel human gene,METTL1,has been identified by its sequence similarity to the yeast ORFYDL201w.The human cDNA and the genomic structure ofMETTL1have been analyzed. The transcript contains 1292 nucleotides and codes for a protein of 276 amino acids. The gene consists of seven exons and extends over 3.5 kb. The six introns vary in length between 93 and 1137 nucleotides. The gene is transcribed in a large variety of organs and tissues and shows differential splicing of two exons, giving rise to at least three different transcripts. TheMETTL1gene was assigned to chromosome 12q13 by radiation hybrid mapping. TheMETTL1gene product shows high sequence similarities to putative proteins from mouse,Drosophila melanogaster, Arabidopsis thaliana, Caenorhabditis elegans,and yeast (39.8% identity between all six species). Computer analyses of the deduced protein sequence reveal two highly conserved amino acid motifs, one of which is typical for methyltransferases. Both motifs are also present in hypothetical proteins from eubacteria. Disruption of the homologous yeast ORFYDL201wshows that the gene is at least not essential for vegetative growth inSaccharomyces cerevisiae.