Biomedical Engineering Reference
In-Depth Information
Genes in eukaryotes are often interrupted by intervening sequences,
introns
,
that must be removed during gene expression. Similarly, rRNAs are produced
from a pre-rRNA that contains so-called internal and external transcribed spac-
ers. These contain regions with characteristic secondary structures (17). RNA
splicing is the process by which these parts are precisely removed from the pre-
mRNA and the flanking, functional exons are joined together (40). Regulated
mechanisms of alternative splicing allow multiple different proteins to be trans-
lated from a single RNA transcript. Mutations can affect splicing of certain in-
trons, leading to abnormal conditions. For example, a form of thalassemia, a
blood disorder, is due to a mutation causing splicing failure of an intron in a
globin transcript, which then becomes untranslatable; see, e.g. (130). The splic-
ing of most nuclear genes is performed by the spliceosome; however, in many
cases the splicing reaction is self-contained, that is, the intron—with the help of
associated proteins—splices itself out of the precursor RNA; see e.g. (93) for a
review.
A textbook example of a functional RNA secondary structure is the
Rho
-
independent termination in
E. coli
. The newly synthesized mRNA forms a hair-
pin in the 3'NTR that interacts with the RNA polymerase, causing a change in
conformation and the subsequent dissociation of the Enzyme-DNA-RNA com-
plex. For a computational analysis of the
Rho
-independent transcription termina-
tors we refer to (162).
Only part of the mature mRNA is translated into a protein. At the beginning
of the mRNA, just behind the cap, is a non-coding sequence, the so-called leader
sequence (10-200 nt), which may be followed by another non-coding sequence
of up to 600 nt. An increasing number of functional features in the untranslated
regions of eukaryotic mRNA have been reported in recent years (67,105).
An extreme example are the Early Noduline genes. Enod40, which is ex-
pressed in the nodule primordium developing in the root cortex of leguminous
plants after infection by symbiotic bacteria (127), codes for an RNA of about
700 nt that gives rise to two short peptides, 13 and 27 amino acids, respectively.
The RNA structure itself exhibits significant conservation of secondary structure
motifs (55), and might take part in localization of mRNA translation (101), as in
the case of the bicoid gene
bcd
of
Drosophila
(87).
2.
RNA SECONDARY STRUCTURES AND THEIR PREDICTION
As with all biomolecules, the function of RNAs is intimately connected to
their structure. It does not come as a surprise, therefore, that most of the classes
of functional RNAs listed in the introduction have, like the well-known
clover-
leaf
structure of tRNAs, distinctive structural characteristics. While successful
predictions of RNA tertiary structure remain exceptional feats, RNA secondary
