Biomedical Engineering Reference
In-Depth Information
o
miRNA
. Micro-RNAs (75,77,80) regulate gene expression by regulating
mRNA expression by a mechanism closely linked to RNA interference by
small double-stranded RNAs (see, e.g. (7,94)). They are cleaved from
their precursors, the small temporal RNAs (
stRNAs
), by the enzyme
Dicer
.
In addition, there is a diverse list of ncRNAs with sometimes enigmatic
function. We give just a few examples (see also the
Rfam
database (41)): the
17-kb
Xist
RNA of humans and the smaller roX RNAs of
Drosophila
play a key
role in dosage compensation and X chromosome inactivation (2,31). Several
large ncRNAs are expressed from imprinted regions. Many of these are cis-
antisense RNAs that overlap coding genes on the other genomic strand (see e.g.
(22)). An RNA (meiRNA) regulates the onset of meiosis in fission yeast (100).
Human vaults are intracellular ribonucleoprotein particles believed to be in-
volved in multi-drug resistance. The complex contains several small untrans-
lated RNA molecules (152). No precise function was known by the summer of
2003 for the human H19 transcript, the hrsX transcript induced by heat shock in
Drosophila
, or the
E. coli
6S RNA, see e.g. (23).
Even though the sequence of the human DNA is known by now, the con-
tents of about half of it remains unknown. The diversity of sequences, sizes,
structures, and functions of the known ncRNAs strongly suggests that we have
seen only a small fraction of the functional RNAs. Most of the ncRNAs are
small, do not have translated ORFs, and are not polyadenylated. Unlike protein
coding genes, ncRNA gene sequences do not seem to exhibit a strong common
statistical signal, hence a reliable general purpose computational genefinder for
non-coding RNA genes has been elusive. It is quite likely therefore that a large
class of genes has gone relatively undetected so far because they do not make
proteins (20).
Another level of RNA function is presented by functional motifs within
protein-coding RNAs. A few of the best-understood examples of structurally
conserved RNA motifs in viral RNAs include:
o
An IRES (internal ribosomal entry site) region is used instead of a CAP to
initialize translation by Picornaviridae, some Flaviviridae including Hepa-
titis C virus, and a small number of mRNAs, see, e.g. (62,105,115).
o
The TAR hairpin structure in HIV and related Retroviruses is the target for
viral transactivation.
o
The RRE structure of Retroviruses serves as a binding site for the Rev
protein and is essential for viral replication. The RRE is a characteristic
five-fingered structural motif, see, e.g. (16).
o
The CRE hairpin (148) in Picornaviridae is vital for replication.
