Abstract
Transcription of transposable elements interspersed in the genome is controlled by complex interactions between their regulatory elements and host factors. However, the same regulatory elements may be occasionally used for the transcription of host genes. One such example is the human L1 retrotransposon, which contains an antisense promoter (ASP) driving transcription into adjacent genes yielding chimeric transcripts. We have characterized 49 chimeric mRNAs corresponding to sense and antisense strands of human genes. Here we show that L1 ASP is capable of functioning as an alternative promoter, giving rise to a chimeric transcript whose coding region is identical to the ORF of mRNA of the following genes: KIAA1797, CLCN5, and SLCO1A2. Furthermore, in these cases the activity of L1 ASP is tissue-specific and may expand the expression pattern of the respective gene. The activity of L1 ASP is tissue-specific also in cases where L1 ASP produces antisense RNAs complementary to COL11A1 and BOLL mRNAs. Simultaneous assessment of the activity of L1 ASPs in multiple loci revealed the presence of L1 ASP-derived transcripts in all human tissues examined. We also demonstrate that L1 ASP can act as a promoter in vivo and predict that it has a heterogeneous transcription initiation site. Our data suggest that L1 ASP-driven transcription may increase the transcriptional flexibility of several human genes.
Highlights
Non-LTR and LTR retrotransposons are the two most abundant classes of transposable elements that contain regulatory regions necessary for their transcription and transposition [9]
Using the strategy described earlier [2] and an updated version of the dbEST (12 May 2004), we extended our search to reveal chimeric transcripts derived from an L1 antisense promoter (ASP) acting as a sole/alternative promoter or driving antisense transcription of host gene
In this paper we show that L1 ASP can cause widespread transcription of human genes and its activity correlates with that of the native promoter in some cases, while in other cases it can expand the tissue-specific expression pattern of the respective gene
Summary
Non-LTR and LTR retrotransposons are the two most abundant classes of transposable elements that contain regulatory regions (promoter, enhancer, and polyadenylation signal) necessary for their transcription and transposition [9]. Scattered all over the chromosomes, retrotransposons can affect the regulation of host genes’ transcription. Recent studies carried out in several laboratories have revealed that LTR retrotransposons, such as an intracisternal A-particle in mice [11], endogeneous retroviruses in humans and mice [12], and Wis 2-1A in wheat [13], can influence transcription of adjacent genes. Two families of non-LTR retrotransposons, L1 [3] and B2 SINE [14], have been shown to drive transcription of human and mouse genes, respectively. It has been shown that the effect of retrotransposons on the host gene expression depends on their epigenetic status and may cause phenotypic variation between genetically identical individuals [15]
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