Cloning and characterization of two overlapping genes in a subregion at 6q21 involved in replicative senescence and schizophrenia

Two new genes were cloned from region 6q21 and characterized. One gene, C6o rf4-6, expresses three mRNA isoforms diverging at the 5' and 3' ends, and e ncodes two protein isoforms that differ by nine amino acids at their amino terminus. The second gene, C6UAS, is transcribed in the antisense orientati on from the complementary strand of C6orf4-6. C6UAS overlaps the second exo n of C6orf4, where the start codon of protein isoform 1 is located. C6UAS h as no apparent ORF and most likely represents a structural RNA gene that is transcribed but not translated. This feature and the antisense polarity of transcription suggest that C6UAS could play a regulatory role on the expre ssion of C6orf4, as indicated by a significant decrease of endogenous C6orf 4 expression after transfection of C6UAS cDNA in human fibroblasts. Neither C6UAS nor C6orf4-6 genes show any homology with known human genes. The two genes were cloned from a subregion at 6q21 containing a replicative senesc ence gene, a tumor suppressor gene and a gene involved in hereditary schizo phrenia. In addition, the common fragile site FRA6F was mapped in the same region. Cloning and characterization of C6orf4-6 and C6UAS may help to clar ify the structure and the functional role of this important region. (C) 200 0 Elsevier Science B.V. All rights reserved.