trans

32 RNA PROCESSING
Caenorhabditis elegans
Evolutionary distance
0.1
Drosophila melanogaster
Schistosoma mansoni
Homo sapiens
Ciona intestinalis
Hydra littoralis
Saccharomyces cerevisiae
Arabidopsis thaliana
Dictyostelium discoideum
Entamoeba histolytica
Trichomonas vaginalis
Encephalitozoon cuniculi
Giardia lamblia
Euglena gracilis
Trypanosoma brucei
FIGURE 2.2 Phylogenetic distribution of SL trans-splicing. Representative species of phyla known to carry out
trans-splicing are boxed in gray. Representative species of phyla in which trans-splicing is absent are in clear boxes.
For those organisms that are unboxed, there is insufficient information to determine the presence or absence of
trans-splicing.
remains an attractive potential target for therapeutic
intervention (see below).
Mechanism of trans-splicing
Prior to considering the biochemical mechanism
of trans-splicing, the process of
cis-splicing will be reviewed briefly since
the mechanisms are related. As noted above,
the vast majority of genes in most eukaryotes
are transcribed as long precursor RNAs which
must be processed to yield translatable mature
mRNAs. Required processing steps include 5
end capping, 3 end cleavage and polyadenylation,
and splicing (the removal of internal
non-coding regions). Extensive biochemical
and genetic analyses in a wide variety of systems
have shown that splicing is catalyzed in
a massive ribonucleoprotein complex known
as the spliceosome. Essential components of
the cis-spliceosome include five small RNAs
(U1, U2, U4, U5 and U6) and more than fifty
proteins. Because the small RNAs function as
RNA–protein complexes, they are known as
MOLECULAR BIOLOGY