HDV Family of Self-Cleaving Ribozymes - Progress in Molecular Biology and Translational Science - page 140

HDV-like ribozymes have now been identified in a plethora of organisms
ranging frommammals, insects, fish, and other deuterostomes to plants, pro-
tists, bacteria, and other viruses.
5.6. Structure-based searches reveal additional HDV ribozymes
outside of mammals
The presence of a conserved HDV ribozyme in mammalian genomes
suggested that the motif might be found in other organisms. Although
in vitro genomic selection could be used to identify the ribozyme in alter-
native organisms, the nature of the experiment is prohibitive to high-
throughput searches for a single RNA motif. Rather, a bioinformatics
methodology can be employed that is capable of analyzing a multitude of
genomes rapidly for a particular catalytic structure.
Bioinformatic searches generally take two forms: sequence- or structure-
based. As mentioned previously, the former has been employed extensively
in mapping organisms' proteomes, while the latter has achieved great success
in identifying noncoding RNAs. In a structure-based search, the identity of
nucleotide or amino acid at a particular location is not as important as the
interactions in which the residue can participate, often with distant portions
of the molecule. Whereas a DNA or RNA sequence-searching algorithm
needs only to match the identity of a particular sequence point-by-point
against the user-specified input, a structure-searching algorithm must first
determine whether a particular structure element can form, and then
whether that element can formwithin the folding space required to produce
the entire motif.
Base pairs dominate the secondary structures of RNA and DNA, and
these interactions should form the basis of any structure-based search. How-
ever, since a helix can form between any base-pairing nucleotides, and the 3 0
sequence is not defined until the 5 0 sequence has been specified, an iterative
search method is required. A number of such iterative search tools exist
including the RNABOB package, which was used to discover numerous
HDV-like ribozymes. 118
RNABOB is an extension of the earlier structure-based search program
RNAMOT that permits the user to describe any RNA structure through an
intuitive “descriptor” design. 115 Helices and single-stranded regions are
independently defined in length, composition, and number of mismatches,
and then they are ordered in relation to each other as they would appear in
the secondary structure ( Fig. 4.6 ). For helices, the user can define either a
specific sequence or allow for any nucleotide, in which case the software will