Biology Reference
In-Depth Information
Abstract
The hepatitis delta virus (HDV) ribozymes are catalytic RNAs capable of cleaving their
own sugar-phosphate backbone. The HDV virus possesses the ribozymes in both sense
and antisense genomic transcripts, where they are essential for processing during rep-
lication. These ribozymes have been the subject of intense biochemical scrutiny and
have yielded a wealth of mechanistic insights. In recent years, many HDV-like ribozymes
have been identified in nearly all branches of life. The ribozymes are implicated in a vari-
ety of biological events, including episodic memory in mammals and retrotransposition
in many eukaryotes. Detailed analysis of additional HDV-like ribozyme isolates will likely
reveal many more biological functions and provide information about the evolution of
this unique RNA.
1. INTRODUCTION
RNAs are responsible for many tasks in the cell, including the trans-
mission of genetic information, ligand binding, and catalysis. RNA enzymes,
ribozymes, include the ribosome and a number of other catalytic RNAs
found both in vivo and in vitro . Among the best-understood ribozymes are
those RNAs capable of self-scission of their own phosphate backbone.
Self-cleaving ribozymes form a diverse set of RNAs that share the com-
mon feature of a 2 0 OH-mediated attack on the phosphodiester of the
adjoining nucleotide to yield a 2 0 -3 0 cyclic phosphate and a 5 0 OH.
Although self-cleaving sequences were first identified for their essential role
in the life cycles of viroids, viruses, and satellite DNA transcripts, mounting
evidence suggests that these sequences are much more widely dispersed in
nature and perform a variety of biological roles. 1-9
The ability to catalyze attack on the phosphodiester backbone is depen-
dent on the RNA's three-dimensional structure. The structure promotes
deprotonation of the attacking 2 0 OH, orienting it for an in-line attack, sta-
bilization of the phosphorane intermediate, and protonation of the 5 0
oxyanion leaving group. Several such catalytic motifs exist, including the
hammerhead, hairpin, hepatitis delta virus (HDV), the Neurospora Varkud
satellite motifs, and the cofactor-dependent glmS ribozyme. 10-14 The
HDV family of ribozymes is the topic of this chapter.
2. HEPATITIS DELTA VIRUS
HDV was first identified in 1977 from clinical isolates of Italian
patients carrying the hepatitis B virus (HBV). 15 HDV is not an autonomous
virus, as it requires a coinfection by fully functional HBV or other helper
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