Abstract
Transposable elements, often considered to be not important for survival, significantly contribute to the evolution of transcriptomes, promoters, and proteomes. Reverse transcriptase, encoded by some transposable elements, can be used in trans to produce a DNA copy of any RNA molecule in the cell. The retrotransposition of protein-coding genes requires the presence of reverse transcriptase, which could be delivered by either non-long terminal repeat (non-LTR) or LTR transposons. The majority of these copies are in a state of “relaxed” selection and remain “dormant” because they are lacking regulatory regions; however, many become functional. In the course of evolution, they may undergo subfunctionalization, neofunctionalization, or replace their progenitors. Functional retrocopies (retrogenes) can encode proteins, novel or similar to those encoded by their progenitors, can be used as alternative exons or create chimeric transcripts, and can also be involved in transcriptional interference and participate in the epigenetic regulation of parental gene expression. They can also act in trans as natural antisense transcripts, microRNA (miRNA) sponges, or a source of various small RNAs. Moreover, many retrocopies of protein-coding genes are linked to human diseases, especially various types of cancer.
Highlights
A large fraction of human and other eukaryotic genomes consist of sequences that originated, directly or indirectly, as a result of transposable elements (TE) activities
Recent analysis of retrocopies derived from circular RNA in the mouse genome has shown long terminal repeats (LTRs) sequences localized in the flanking regions, which may suggest LTR-mediated retrotransposition [45]
The ribonucleoprotein particle formed by RNA and LINE1-encoded proteins needs to get close to the chromosome DNA, where the target-primed reverse transcription occurs
Summary
A large fraction of human and other eukaryotic genomes consist of sequences that originated, directly or indirectly, as a result of transposable elements (TE) activities. Reverse transcriptase (RT), encoded by some TEs, can be used in trans to produce a DNA copy of any RNA molecule in the cell This copy, reintegrated into the genome, will most likely be “dead on arrival” because none of the regulatory elements can be copied in RNA-mediated gene duplication. The functional mouse retrogene Rps23r1 reduces Alzheimer’s beta-amyloid levels and tau phosphorylation [10] This particular retrogene is rodent-specific and does not exist in the human genome. Another elegant example of the functional phenotypic effect of retroposition was demonstrated by fgf retrogene studies. We present recent studies aiming to decipher the functions of transcriptionally active retrocopies of protein-coding genes
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