Structural diversity of self-cleaving ribozymes

AUTOR(ES)

Tang, Jin

FONTE

The National Academy of Sciences

RESUMO

In vitro selection was used to isolate Mg2+-dependent self-cleaving ribozymes from random sequence. Characterization of representative clones revealed the emergence of at least 12 classes of ribozymes that adopt distinct secondary structure motifs. Only one class corresponds to a previously known structural motif, that of the naturally occurring hammerhead ribozyme. Each ribozyme promotes self-cleavage via an internal phosphoester transfer reaction involving the adjacent 2′-hydroxyl group with a chemical rate enhancement of between 103- and 106-fold greater than the corresponding uncatalyzed rate. These findings indicate that RNA can form a multitude of secondary and tertiary structures that promote cleavage by internal phosphoester transfer. Upon further in vitro selection, a class I ribozyme that adopts an “X motif” structure dominates over all other ribozymes in the population. Thus, self-cleaving RNAs isolated by in vitro selection from random-sequence populations can rival the catalytic efficiency of natural ribozymes.

Documentos Relacionados

• Selection of novel Mg(2+)-dependent self-cleaving ribozymes.
• Chrysanthemum chlorotic mottle viroid: Unusual structural properties of a subgroup of self-cleaving viroids with hammerhead ribozymes
• Mutagenesis analysis of a self-cleaving RNA.
• Selection of targets and the most efficient hairpin ribozymes for inactivation of mRNAs using a self-cleaving RNA library
• RNA stem stability in the formation of a self-cleaving hammerhead structure.