CANINE U2 SNRNA GENE - NUCLEOTIDE-SEQUENCE, CHARACTERIZATION AND IMPLICATIONS IN RNA PROCESSING AND CANCER BIOLOGY

Abnormal RNA processing (splicing) may lead a cell to become cancerous . Transcription of a gene starts in the nucleus where genomic DNA is c onverted to precursor RNA by removing introns and joining exons. Splic ing, mediated by small nuclear RNA (snRNA) and nuclear proteins, is ti ghtly regulated during growth and development. U2 snRNAs are small, st able RNAs located in the nucleus of eukaryotic cells that recognize th e branch point of the intron-exon junction. We describe here the organ ization of DNA sequences complementary to canine U2 snRNA. From a geno mic library we isolated one recombinant containing the U2 gene. Southe rn analysis revealed that the canine species possesses only 3 to 5 U2 snRNA genes or very closely related sequences. The size of the U2 gene is 125 nt whereas in rat, Drosophila, trypanosome and yeast it is 189 , 234, 141, and 192 nt respectively. The nucleotide sequence showed 82 , 78, 72 and 95% homology with rat, Drosophila, yeast, and trypanosome U2 snRNA, respectively. The sensitivity of U2 snRNA towards alpha-ama nitin suggests that it is transcribed by RNA polymerase II, The conser ved nucleotide sequences which have been implicated in heterogeneous n uclear RNA splicing have been identified. The implications of the know ledge gained through above studies in cancer biology are discussed.