Biology Reference
In-Depth Information
Very little is known about posttranscriptional regulation of Alu and
SVA elements. In the case of Alu it is mainly due to the technical difficulties
associated with the detection of the endogenous Alu transcripts produced
through Pol-III vs. Pol-II transcription. Alu inserts are enriched within human
genes (Lander
, 2001), and, as a result, they are transcribed as a part of
numerous cellular mRNAs. This makes it extremely challenging to delineate
authentic Pol-III Alu-promoted transcripts from Pol-II generated transcripts. It is
known that, following transcription, many Alu transcripts appear to be processed
into small cytoplasmic (scAlu) transcripts, which, based on genomic sequence
data, exhibit greatly reduced retrotransposition efficiency (Shaikh
et al.
, 1997).
Although a subset of these scAlus can be attributable to the introduction of
cryptic Pol-III termination sites, it is unclear whether the remainder are gener-
ated by simple degradation or a more active process (Shaikh
et al.
, 1997).
Another reported mechanism that acts downstream of transcription but at the
unidentified step in the TE life cycle is down regulation of TE retrotransposition
by the APOBEC family of proteins (Chiu
et al.
et al.
, 2006; Hulme
et al.
, 2007;
Muckenfuss
, 2006; Stenglein and Harris, 2006). Members of this family
of proteins exhibit differential effects on L1 and Alu retrotransposition, high-
lighting the differences in some yet unknown requirements between mobiliza-
tions of the two human retroelements.
The complicated and dynamic nature of the TE-host coexistence is
further supported by the observation that artificial upregulation of L1 expression
through stable L1 transfection in HeLa cells significantly decreases retrotranspo-
sition of both L1 and Alu elements in these cells (Wallace
et al.
, 2010). The
phenomenon appears to correlate with the levels of stably expressed L1 ORF2
protein and the presence of the functional L1 EN domain (Wallace
et al.
, 2010).
Adaptation of the cellular DNA repair machinery to handle the L1-induced
DNA double-strand breaks is implicated as a primary cause of the reduced L1 and
Alu retrotransposition in cancer cells overexpressing functional L1. Because of
the usage of artificial levels of L1 expression in this experimental system it is not
immediately clear what thresh-hold levels of endogenous L1 expression need to
be bypassed to institute a similar phenomenon
et al.
. Nevertheless, these data
strongly suggest that the interplay between TEs and their host is likely an ever-
changing process and should be viewed as such, particularly when considering TE
expression and activity in cells with genetic defects (Morrish
in vivo
, 2002) or cells
exposed to environmental stimuli known to affect TE activity (Kale
et al.
et al.
, 2005,
2006).
It is obvious from the above examples that keeping TE expression at bay
is an important priority for the normal cellular existence. This significance is
further supported by the data collected in cultured cells that show that ectopic L1
expression causes significant toxicity in both normal and cancer cells (Belancio
et al.
, 2010b; Gasior
et al.
, 2006; Wallace
et al.
, 2008b), indicating that each cell
