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 converted to precursor RNA by removing introns and joining exons. Splicing, mediated by small nuclear RNA (snRNA) and nuclear proteins, is tightly regulated during growth and development. U2 snRNAs are small, stable RNAs located in the nucleus of eukaryotic cells that recognize the branch point of the intron-exon junction. We describe here the organization of DNA sequences complementary to canine U2 snRNA. From a genomic library we isolated one recombinant containing the U2 gene. Southern 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-amanitin suggests that it is transcribed by RNA polymerase II. The conserved nucleotide sequences which have been implicated in heterogeneous nuclear RNA splicing have been identified. The implications of the knowledge gained through above studies in cancer biology are discussed.