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Review
. 2017 Apr 13;9(4):80.
doi: 10.3390/v9040080.

Protein-Coding Genes' Retrocopies and Their Functions

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Free PMC article
Review

Protein-Coding Genes' Retrocopies and Their Functions

Magdalena Regina Kubiak et al. Viruses. .
Free PMC article

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.

Keywords: gene duplication; genome evolution; retrocopy; retrogene; retrotransposition; retrotransposon.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the structural organization of (a) long terminal repeat (LTR) and (b) non-LTR retrotransposons. A detailed description can be found in Section 2.2 and Section 2.3.
Figure 2
Figure 2
Genomic fractions of retrotransposons in selected genomes. Based on: Zea mays [23], Hordeum vulgare [25], Drosophila melanogaster, Mus musculus (genome version mm10), Homo sapiens (genome version hg38)—Repeat Masker online dataset [28].
Figure 3
Figure 3
Model of mRNA retrotransposition mediated by the LTR retrotransposon (based on [20,44,51]). The blue sphere represents the nucleus. Stages: 1: Transcription of the LTR retrotransposon (LTR) and parental gene (PG). 2: Translation of LTR-encoded proteins, including reverse transcriptase (RT), integrase (IN), and proteins building virus-like particles (VLPs). 3: Formation of VLP with LTR-derived mRNA and parental gene mRNA. 4: Reverse transcription and template switch (TS). 5: Formation of the cDNA-IN complex. 6: Translocation and integration of chimeric cDNA into the genome.
Figure 4
Figure 4
Model of mRNA retrotransposition mediated by non-LTR retrotransposon referring to LINE1. The blue sphere represents the nucleus; the dotted line shows the probability of nucleus membrane disruption. Description of the stages: 1: Transcription of the non-LTR retrotransposon (non-LTR) and parental gene (PG). 2: Translation of non-LTR–encoded proteins, including proteins with reverse transcriptase (RT) and endonuclease (EN) domains and RNA-binding proteins with chaperone activity. 3: Formation of ribonucleoprotein particle by binding of the proteins to the polyA tail of the parental gene mRNA. 4: Transport of ribonucleoprotein particle near the genome. 5: Reverse transcription and incorporation of the parental gene.
Figure 5
Figure 5
Selected functions of retrogenes. (a) On the DNA level, for example, retrogenes may be used as alternative exons and create chimeric transcripts or be involved in transcriptional interference; (b) as RNAs, they can participate in epigenetic regulation of parental gene expression and act as trans-natural antisense transcripts, microRNA (miRNA) sponges or a source of various small RNAs; (c) retrogenes can also encode proteins, which might retain the parental gene function (subfunctionalization), evolve a new function (neofunctionalization), or even functionally replace the parental gene (“orphan” retrogenes).

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