Biology Reference
In-Depth Information
of transcripts through RNAPol-II in the case of L1mRNAand Pol-III in the case of
Alu, as well as the association with the cellular translation machinery (neither Alu
nor SVA transcripts are believed to contain any ORFs; Kroutter
,2009).
Interestingly, an artificial switch from Pol-III to Pol-II generated Alu transcripts
results in the requirement of ORF1 for Alu mobilization (Kroutter
et al.
,2009).
The multistep life cycle of human TEs provides ample opportunities for
the host to erect barriers that would allow prevention of efficient amplification of
TEs. Understanding of the TE life cycle makes it very clear that suppression of
TE expression can be a very effective way of minimizing their negative impact on
the genome stability.
et al.
B. TE expression
TEs are families of elements interspersed throughout the human genome, as a
result, each of human TEs is represented by hundreds or thousands of nonidentical
loci that can be expressed in any given cell (Lander
, 2001). Thus, endoge-
nous expression detected by conventional techniques is usually a combination of
transcripts produced by a subpopulation of loci expressed in the assessed cell type.
Due to the sequence variation among the majority of TE loci found in the human
genome, each method used to analyze TE expression is often accompanied by its
own set of specific detection biases, discussion of which is beyond the scope of this
review. Technical difficulties associated with detection of human TEs combined
with the presumed relatively low expression levels and incomplete knowledge of
rules governing TE expression have accounted for the impediment of progress in
this area of TE research. The expression of endogenous L1 elements (mRNA and
ORF1 protein) was reported to be restricted to the mouse germline (Branciforte
and Martin, 1994; Ostertag
et al.
, 2002). The expression of the L1 proteins was
also detected in specific somatic cell types (such as Leydig, Sertoli, and vascular
endothelial cells; Ergun
et al.
.,
1996). Analysis of endogenous L1 expression in various types of human tumors
and cancer cell lines established that L1 expression, as a rule, is significantly
upregulated in human malignancies (Bratthauer and Fanning, 1992, 1993;
Bratthauer
et al.
, 2004) and in normal breast tissues (Asch
et al
, 1994). As is obvious from the TE life cycle (described above),
ongoing L1 expression is necessary for the activity of Alu and SVA elements.
Even though it is deduced from the Alu and SVA retrotransposition events
occurred in the germline that both of these elements are expressed at minimum
in the germline, the endogenous expression of Alu and SVA elements is very
poorly characterized (Fuhrman
et al.
, 1997). Few studies have
attempted to assess Alu transcripts in a manner that distinguishes Pol-II- and
Pol-III- promoted transcripts (Shaikh
et al.
, 1981; Shaikh
et al.
et al.
, 1997).
