A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian genomes

Brandt, Jürgen; Veith, Anne-Marie; Volff, Jean Nicolas

doi:10.1159/000084963

Cited by 67 publications

(102 citation statements)

References 148 publications

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“…(39) The mechanistic similarities between epigenetic control of transposition and genomic imprinting suggest that the epigenetic regulation of certain imprinted domesticated genes might be derived from the defence mechanims having repressed the activity of the ancestral transposable element. (73) Transposable element-derived genes have been observed in diverse eukaryotic lineages including animals, plants and fungi, and some of them fulfil functions essential to their host. Some events of domestication are probably very ancient and might coincide with or even predate the apparition of eukaryotes.…”

Section: Discussionmentioning

confidence: 99%

“…(72) It has been speculated that this type of regulation might be derived from the epigenetic mechanisms having repressed the ancestral LTR retrotransposon. (73) Three Mart proteins have conserved the zinc finger domain present in the original Gag protein, suggesting a function involving binding to nucleic acids. Indeed, Mart2 (aka Myef-3) has been described as a transcription factor potentially regulating the expression of the myelin basic protein gene in the mouse.…”

Section: Telomerase and Its Relationship To Retrotransposon Reverse Tmentioning

confidence: 99%

“…(74) Two Mart genes have conserved the À1 translational frameshift present between gag and pol in the original LTR retrotransposon. (66,73) Some Mart genes are differentially expressed in cancer cells and might be involved in the control of cell proliferation and apoptosis. (75,76) .…”

Section: Telomerase and Its Relationship To Retrotransposon Reverse Tmentioning

confidence: 99%

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Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes

2006

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Autonomous transposable elements, generally considered as junk and selfish, encode transposition proteins that can bind, copy, break, join or degrade nucleic acids as well as process or interact with other proteins. Such a repertoire of activities might be of interest for the host cell. There is indeed substantial evidence that mobile DNA can serve as a dynamic reservoir for new cellular functions. Transposable element genes encoding transposase, integrase, reverse transcriptase as well as structural and envelope proteins have been repeatedly recruited by their host during evolution in most eukaryotic lineages. Such domesticated sequences protect us against infections, are necessary for our reproduction, allow the replication of our chromosomes and control cell proliferation and death; others are essential for plant development. Many new candidates for domesticated sequences have been revealed by sequencing projects. Their functional analysis will uncover new aspects of evolutionary alchemy, the turning of junk into gold within genomes.

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Section: Discussionmentioning

confidence: 99%

Section: Telomerase and Its Relationship To Retrotransposon Reverse Tmentioning

confidence: 99%

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Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes

2006

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“…Before this study, RGAG1and APOLD1 were not known to be epigenetically silenced in cancers. RGAG1 (also known as MART9) is an X-linked retrotransposon-derived neogene of unknown function (Brandt et al, 2005). Expressed sequence tags of RGAG1 were found predominantly in the testis, suggesting that this retrogene might be important in germ cell development.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer

et al. 2010

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BACKGROUND: Testicular germ cell tumour (TGCT) is the most common malignant tumour in young males. Although aberrant DNA methylation is implicated in the pathophysiology of many cancers, only a limited number of genes are known to be epigenetically changed in TGCT. This report documents the genome-wide analysis of differential methylation in an in vitro model culture system. Interesting genes were validated in TGCT patient samples. METHODS: In this study, we used methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to identify differentially methylated regions (DMRs). RESULTS: We identified 35 208 DMRs. However, only a small number of DMRs mapped to promoters. A genome-wide analysis of gene expression revealed a group of differentially expressed genes that were regulated by DNA methylation. We identified several candidate genes, including APOLD1, PCDH10 and RGAG1, which were dysregulated in TGCT patient samples. Surprisingly, APOLD1 had previously been mapped to the TGCT susceptibility locus at 12p13.1, suggesting that it may be important in TGCT pathogenesis. We also observed aberrant methylation in the loci of some non-coding RNAs (ncRNAs). One of the ncRNAs, hsa-mir-199a, was downregulated in TGCT patient samples, and also in our in vitro model culture system. CONCLUSION: This report is the first application of MeDIP-chip for identifying epigenetically regulated genes and ncRNAs in TGCT. We also demonstrated the function of intergenic and intronic DMRs in the regulation of ncRNAs.

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“…It is perhaps not surprising that a proportion of them also utilize frameshifting, which is well known in the decoding of retroviruses and, to an increasing extent, in retroelements (31,34), including in mammalian cells (35), yeast (36), and Drosophila (37).…”

Section: Discussionmentioning

confidence: 99%

A Functional –1 Ribosomal Frameshift Signal in the Human Paraneoplastic Ma3 Gene

Wills

Moore

Hammer

et al. 2006

Journal of Biological Chemistry

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A bioinformatics approach to finding new cases of ؊1 frameshifting in the expression of human genes revealed a classical retroviruslike heptanucleotide shift site followed by a potential structural stimulator in the paraneoplastic antigen Ma3 and Ma5 genes. Analysis of the sequence 3 of the shift site demonstrated that an RNA pseudoknot in Ma3 is important for promoting efficient ؊1 frameshifting. Ma3 is a member of a family of six genes in humans whose protein products contain homology to retroviral Gag proteins. The ؊1 frameshift site and pseudoknot structure are conserved in other mammals, but there are some sequence differences. Although the functions of the Ma genes are unknown, the serious neurological effects of ectopic expression in tumor cells indicate their importance in the brain.Although nonoverlapping triplet reading of mRNA codons is the essence of genetic decoding, dynamic nonstandard events at specific sites can permit product diversity and provide regulatory options. One of these recoding events involves shifting to an alternative reading frame by a proportion of ribosomes, thereby changing the linearity of readout. Such utilized frameshifting commonly features both a "shifty site" in the mRNA and an appropriately positioned structural feature in the mRNA that acts to enhance the level of frameshifting, i.e. it is programmed. Although the shift involved can be to either alternative frame, a shift to the Ϫ1 frame often involves tRNAs in both the A and P sites detaching from their codons and re-pairing to mRNA at the two overlapping Ϫ1 frame codons (1, 2). This tandem detachment and re-pairing usually occurs on a "slippery" heptanucleotide sequence that follows the general pattern of X XXY YYZ where the A and P site tRNAs detach from the zero frame codons XXY YYZ and re-pair after shifting 1 nucleotide to XXX YYY. The spacer region between the shift site and the 3Ј structural element is commonly 6 -8 nt 2 (3). The most common 3Ј recoding signals for Ϫ1 frameshifting are pseudoknots (4, 5) with distinct features (6, 7). A less common type of pseudoknot is the kissing stem-loop found in the human coronavirus, HCV229E (8), but bioinformatic studies suggest that it may be involved for transmissible gastroenteritis virus frameshifting also (9).Examples of genes that require Ϫ1 frameshifting for expression are well known in viral genomes. There is only one demonstrated case of Ϫ1 frameshifting in a mammalian cellular gene (10, 11), but it does not display the phylogenetic breadth of the ϩ1 frameshifting utilized in decoding antizyme mRNA, conserved from mammals to yeasts (12). Frameshifting near the end of a coding sequence often allows a proportion of ribosomes to access an ORF that extends beyond the zero frame terminator so that the transframe (coupled ORF) protein is longer than that of standard decoding. The easiest class of Ϫ1 programmed frameshift events to search for is one that has conserved architecture of two ORFs that partially overlap and contains a defined shift site. In these cases conser...

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A family of neofunctionalized Ty3/gypsy retrotransposon genes in mammalian genomes

Cited by 67 publications

References 148 publications

Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes

Turning junk into gold: domestication of transposable elements and the creation of new genes in eukaryotes

Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer

A Functional –1 Ribosomal Frameshift Signal in the Human Paraneoplastic Ma3 Gene

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