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as mouse testis, spleen, and brain tissues. 2 Although uncorroborated, it is
likely that the ribozyme undergoes self-cleavage in human brain isolates
as CPEB3 is expressed at the RNA level in brain and likely plays a role
in synaptic plasticity. 101,104 Ribozyme expression was also observed in
mouse ovaries, kidneys, lungs, skeletal muscle, and bone marrow. 105
Reverse transcription followed by quantitative polymerase chain reac-
tion (RT-qPCR) performed on murine tissues revealed the cleavage state
of the ribozyme to be tissue specific. 105 For example, in skeletal muscle
CPEB3 mRNA expression is high; however, the intron must be efficiently
processed prior to ribozyme cleavage because no ribozyme-containing
mRNAs are detected. 105 Alternatively, self-cleaved forms of the ribozyme
are readily detected in ovarian and kidney tissues. Together, these data allude
to the existence of an unknown regulatory mechanism for controlling both
ribozyme-catalyzed self-scission and CPEB3 expression.
Although the effects of the ribozyme self-cleavage are largely unknown,
the CPEB3 ribozyme appears to have an effect on episodic memory in
humans. 106 A subset of human ribozyme isolates contain a single-nucleotide
polymorphism (SNP) that changes the G-U wobble pair at the cleavage site
to a G-C Watson-Crick pair. This mutation has been demonstrated to
increase the overall rate of catalysis by approximately threefold. 2 Individuals
homozygous for this SNP (rs11186856) experience decreased delayed epi-
sodic memory and specifically encounter difficulty recalling words and
instances that have a high emotional valence (e.g., joy, poverty). 106 These
findings suggest that the ribozyme may have a role in the neurobiology
of emotional memory.
5.5. Bioinformatic identification of ribozymes
The CPEB3 ribozyme is the first instance of an HDV-like self-cleaving
RNA found outside of the namesake organism. 2,3 Other ribozyme motifs,
specifically hammerhead ribozymes, have been readily detected in numer-
ous organisms following their initial identification. 1,5,6,107-110 This contrast
is likely due to several factors. First, the hammerhead motif is much less
informationally complex than that of the HDV ribozymes. The genomic
HDV molecule has an information content of approximately 50-55 bits,
whereas a typical hammerhead sequence carries only 44 bits of information.
This difference in complexity is reflected in current sequence data, where
the hammerhead-like motifs are detected two orders of magnitude more fre-
quently than HDV-like motifs when using comparable structure-based
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