U1 snRNA: the evolution of its primary and secondary structure.

In this paper we first show that the primary structure of U1 snRNA is homologous to that of tandem repeated pre-tRNA. Two sets of polymerase III promoter sites (the a and b boxes) are clearly recognisable at the appropriate positions in U1, although neither is functional; these sites occur in a degenerate form and their transcription is initiated by polymerase II. Moreover, several of the conserved subsequences of tRNAs that are not associated with transcription initiation (and supposedly are conserved because of their role in translation) are conserved in U1 as well, one of them being the pattern Py-Py-anticodon-Pu-Pu (for both anticodons of tandem tRNA). Second, we show that the secondary structure of U1 is apparently formed after fixation of the "B-hairpin loop' by one of the associated proteins. If and only if this hairpin loop is fixed, a consensus secondary structure is produced by the minimisation-of-free-energy technique. Moreover, we show that this B-hairpin loop has been destabilised relatively recently in evolutionary time by deletions (e.g., in the polymerase III box). If we reinsert the deleted bases, the so constructed hypothetical "ancestral" molecule folds into the consensus secondary structure by unconstrained energy minimisation (i.e., without fixation of the B-loop). Some features of the secondary structure of tandem repeated pre-tRNA are conserved in U1, but the overall structure has changed dramatically. Like tRNA, U1 has a cloverleaf-like structure, but its overall size has doubled. By comparing their secondary structures and by alignment of the sequences, we trace the local events associated with the global change in secondary structure (and apparently in the function of the molecule). Finally, we discuss our results from the perspective of informatic prerequisites for heterarchical multilevel evolution.