Trans hammerhead ribozyme: Ligation vs. cleavage

Abstract

Trans hammerhead ribozymes are considered from the point of view of the RNA world theory. An attempt was made to reconstruct the 'ancestors' of contemporary hammerhead ribozymes with improved ligation activity by altering the sequence of trans hammerhead motifs. RNA ligation activity of trans hammerheads was shown to be affected significantly by minor changes in non-conservative regions. In particular, introduction of heptanucleotide bulge into stem III led to the 10-fold increase of ligation rate constant. At that, RNA cleavage was predominant activity in all cases. It was shown that trans hammerhead ribozyme can assemble from two separate short oligoribonucleotides upon binding to RNA substrate. This binary hammerhead ribozyme possesses a higher RNA-cleaving activity than its full-length analog. It can be assumed that such self-assembling multi-subunit catalytic RNAs could exist at early stages of the prebiotic evolution. © Springer 2008.