Primary and secondary structures of chicken, rat and man nuclear U4 RNAs. Homologies with U1 and U5 RNAs.

U4 RNA from chicken, rat and man was examined for nucleotide sequence and secondary structure. Three molecular species, U4A, U4B and U4C were detected in the three animal species. U4A is 146 nucleotide long and U4B RNA only lacks the 3' terminal G. four nucleotides are missing at the 3'-end of U4C RNA which, in addition, differs from U4A and U4B RNAs at two internal positions. Thus, U4C RNA is encoded by another gene as U4A and U4B RNAs. Only one nucleotide substitution occurred between chicken and man showing that U4A, U4B and U4C RNAs have been extremely conserved throughout evolution. The three molecular species are capped, they contain three psi, a 2'-P methyl A and a m6A. An additional post-transcriptional modification close to the cap structure is observed in man. On the basis on an experimental study, two models of secondary structure may be proposed for U4 RNA. The 3'domain is the same in both models and is homologous to that of U1 and U5 RNAs. It consists of a single-stranded region, containing the sequence Py-(A)2-(U)n-Gp flanked by two stable hairpins probably involved in tertiary interactions. The 5' domain is less stable than the 3' domain and its structure is different in the two models. However, a long single-stranded pyrimidine region containing modified nucleotides is found in both models as in U1 and U5 RNAs. Several other nucleotide sequence homologies related to specific features of secondary structure suggest that U1, U4 and U5 RNAs derive from a common ancestor and may have common function.