Biology Reference
In-Depth Information
The outcome of one RNA processing event can affect the outcome of others
resulting in regulatory 'networks' that influence both the information content
and expression of the 'ribotype' (RNA pool), which in turn influences pheno-
type. Alterations in RNA processing generate different sets of ribotypes which
are subject to natural selection on the basis of the phenotypes they produce.
The evolutionary process requires the preservation of successful ribotypes in
an inheritable (
sic
) form.
3.2.2 Aberrant transcripts
There are numerous examples in the literature of aberrantly processed mRNA
transcripts being produced in addition to correctly processed mRNAs in the cells
of normal healthy individuals (Berg
et al
., 1996). It is possible that some of these
'aberrant transcripts' could be of functional significance but in the majority of
cases they are likely to occur simply as a consequence of the absence of any selec-
tive pressure to avoid aberrant splicing. One example of this phenomenon is pro-
vided by the human glutathione peroxidase type 5 (
GPX5
) gene in which the
majority of gene transcripts appear to be incorrectly spliced (Hall
et al
., 1998). If
taken to its extreme, however, and the extent of aberrant splicing increases
beyond a certain point, a gene may come to be effectively inactivated as has
occurred in the case of the human chorionic somatomammotropin (
CSHL1
;
17q22-q24) 'pseudogene' (Misra-Press
et al
., 1994).
3.2.3 mRNA surveillance
The cell does however possess a mechanism that is capable of removing those aber-
rant transcripts that encode 'nonsense mRNAs' which would otherwise be expected
to give rise to truncated proteins. Such mRNAs are often inherently unstable as a
result of a process known as
mRNA surveillance
which involves nonsense-mediated
mRNA decay (Culbertson, 1999). mRNA surveillance appears to be ubiquitous in
eukaryotes with homologous proteins encoded by orthologous genes being found in
organisms as widely separated as yeast (Upf1, Upf2, Upf3) and human (
RENT1
;
19p13; Culbertson, 1999). Presumably this mechanism has evolved in order to
reduce the cost to the cell of producing non-productive transcripts.
3.2.4 Ectopic transcripts
Extremely low levels of correctly spliced mRNA transcripts from tissue-specific
genes have been demonstrated in supposedly 'non-expressing' cell types
(reviewed by Cooper
et al
., 1994). Such
ectopic
or
illegitimate
transcripts have been
found to occur at levels as low as one mRNA molecule per 500-1000 cells, >1000-
fold lower than the level of an average 'low abundance' mRNA. It remains unclear
whether every cell is capable of generating ectopic transcripts or alternatively if
the occasional cell in an otherwise non-expressing tissue is able to produce com-
paratively high levels of the transcript in question. Do ectopic transcripts have a
biological role? Since the levels involved are often extremely low, it is hard to
imagine that such a role involves significant protein synthesis. Perhaps what we
observe simply represents a reasonable balance between the cost to the cell of
