A comparison of genomic structures and expression patterns of two closely related flanking genes in a critical lung cancer region at 3p21.3

In the search for a tumour suppressor gene in the 3P21.3 region we isolated two genes, RBM5 and RBM6. Gene RBM5 maps to the region which is homozygous ly deleted in the small cell lung cancer cell line GLC20; RBM6 crosses the telomeric breakpoint of this deletion, Sequence comparison revealed that at the amino acid level both genes show 30% identity, They contain two zinc f inger motifs, a bipartite nuclear signal and two RNA binding motifs, sugges ting that the proteins for which RBM5 and RBM6 are coding have a DNA/RNA bi nding function and are located in the nucleus. Northern and Southern analys is did not reveal any abnormalities. By SSCP analysis of 16 lung cancer cel l lines we found only in RBM5 a single presumably neutral mutation, By RT-P CR we demonstrated the existence of two alternative splice variants of RBM6 , one including and one excluding exon 5, in both normal lung tissue and lu ng cancer cell lines, Exclusion of exon 5 results in a frameshift which wou ld cause a truncated protein of 520 amino acids instead of 1123 amino acids . In normal lung tissue, the relative amount of the shorter transcript was much greater than that in the lung tumour cell lines, which raises the ques tion whether some tumour suppressor function may be attributed to the deriv ed shorter protein.