Substitutions, insertions, and deletions in two highly conserved U3 RNA species

In view of the increasing interest in low molecular weight ribonucleoprotein particles in exon-intron binding and cleavage reactions (Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L., and Steitz, J. A. (1980) Nature 283, 220--224), the complementarity of the conserved regions to HnRNAs, or protein binding sites, or both, is of potential importance. U3A, U3B, and U3C are three RNA species localized to the nucleolus of Novikoff hepatoma cells. The nucleotide sequence of U3A RNA determined in this study was compared to that of U3B RNA (Reddy, R., Henning, D., and Busch, H. (1979) J. Biol. Chem. 254, 11097--11105). Both U3A and U3B RNAs contained 5' "caps" and were 216 nucleotides long. The nucleotide sequence 1 to 87 was identical in both U3A and U3B, but differences were found at 18 positions in the remainder of the sequence. Of these differences, 11 were single base replacements, two were dinucleotide replacement AU leads to GG at positions 93 to 94, UC leads to GG at positions 173 to 174, and one was a trinucleotide replacement, UCG leads to CUU at positions 179 to 181. Of the total 18 base replacements, 11 (61%) were purine leads to purine or pyrimidine leads to pyrimidine. Interestingly, two base insertions/deletions were found in each RNA when both RNA sequences were compared for maximum sequence similarity. These data establish that the heterogeneity of some low molecular weight nuclear and nucleolar RNA species resulted from a small number of mutations but much of the sequence was conserved.