Biomedical Engineering Reference
In-Depth Information
their interactions at a genomic level, is of utmost practical and theoretical impor-
tance in modern life sciences. A comprehensive understanding of the biology of
a cell obviously requires the knowledge of the identity of
all
encoded RNAs, the
molecules with which they interact, and the molecular structures of these com-
plexes (18).
Structural genomics, the systematic determination of all macromolecular
structures represented in a genome, until very recently has been focused almost
exclusively on proteins. Although it is commonplace to speak of "
genes and
their encoded protein products
," thousands of human genes produce transcripts
that exert their function without ever producing proteins. The list of functional
non-coding RNAs (ncRNAs) includes key players in the biochemistry of the
cell. Many of them have characteristic secondary structures that are highly con-
served in evolution. Databases (referenced below) collect the most important
classes:
o
tRNA
. Transfer RNAs are the adapters that translate the triplet nucleic
acid code of RNA into the amino acid sequence of proteins (128).
o
rRNA
. Ribosomal RNAs are central to the translational machinery. Re-
cent results strongly indicate that peptide bond formation is catalyzed by
rRNA (46,89,103,132,150).
o
snoRNA
. Small nucleolar RNAs are required for rRNA processing and
base modification in the eukaryotic nucleolus (102,116).
o
snRNA
. Small nuclear RNAs are critical components of spliceosomes, the
large ribonucleoprotein complexes that splice introns out of pre-mRNAs
in the nucleus (161).
o
tmRNA
. The bacterial tmRNA (also known as 10Sa RNA or SsrA) was
named for its dual tRNA-like and mRNA-like nature. tmRNA engages in a
translation process, adding in trans a C-terminal peptide tag to the unfin-
ished protein at a stalled ribosome. The tmRNA-directed tag targets the
unfinished protein for proteolysis (146,160).
o
RNase P
. Ribonuclease P is responsible for the 5'-maturation of tRNA
precursors. Ribonuclease P is a ribonucleoprotein, and in bacteria (and
some Archaea) the RNA subunit alone is catalytically active in vitro, i.e.,
it is a ribozyme (8). RNase MRP, which shares structural similarities with
RNase P RNA, cleaves at a specific site in the precursor-rRNA transcript
to initiate processing of the 5S rRNA.
o
telRNA
. Telomerase RNA. Telomeres are the specialized DNA protein
structures at the ends of eukaryotic chromosomes. Telomerase is a ribonu-
cleoprotein reverse transcriptase that synthesizes telomeric DNA (6).
o
SRPRNA
. The signal recognition particle is a universally conserved ribo-
nucleoprotein. It is involved in the co-translational targeting of proteins to
membranes (37).
