Giant Reverse Transcriptase-Encoding Transposable Elements at Telomeres

Arkhipova, Irina R.; Yushenova, Irina A.; Rodríguez, Fernando

doi:10.1093/molbev/msx159

Cited by 34 publications

(44 citation statements)

References 63 publications

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“…In some species, the telomeres are in fact a piRNA-generating locus. For example, piRNAs are produced from telomere-integrated retrotransposons in flies, silkworms as well as the large TEs known as “terminons” in the telomeres of rotifers {Arkhipova, 2017}. Small RNA molecules described as piRNA-like RNAs have been reported to derive from mouse telomeres {Cao, 2009}.…”

Section: Discussionmentioning

confidence: 99%

Endogenization and excision of human herpesvirus 6 in human genomes

Liu

Kosugi

Koide

et al. 2019

Preprint

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36The genome of human herpesvirus 6 (HHV-6) is integrated within the nuclear genome of 37 about 1% of humans, but how this came about is not clear. HHV-6 integrates into telomeres, 38 and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is 39 located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-40interacting RNAs (piRNAs). piRNAs block integration of transposons in the germline, so 41 piRNA-mediated repression of HHV-6 integration has been suspected. Whether integrated 42 HHV-6 can reactive into an infectious virus is also uncertain. In vitro, recombination of the 43 viral genome along its terminal direct repeats (DRs) leads to excision from the telomere and 44 viral reactivation, but the expected single DR "scar" has not been described in vivo. We 45 analyzed whole-genome sequencing (WGS) data from 13,040 subjects, including 7,485 from 46 Japan. We found an association between integrated HHV-6 and polymorphisms on chr22q in 47Human herpesvirus 6 (HHV-6) infects most people during childhood, usually only causing 63 fever and rash. Reactivation of HHV-6 has been linked to a number of neurological diseases 64 including encephalitis, Alzheimer's disease and multiple sclerosis. However, about 1% of 65 people are born with the HHV-6 genome present within their genome, included in the end 66"cap" of one of their 46 chromosomes. Little is known about how and when HHV-6 genomes 67 entered human genomes, whether or not they still do, and whether or not this poses risk for 68 virus reactivation. We looked for HHV-6 in genome sequences from over 13,000 people. 69

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Section: Discussionmentioning

confidence: 99%

Endogenization and excision of human herpesvirus 6 in human genomes

Liu

Kosugi

Koide

et al. 2019

Preprint

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“…APE endonucleases have been shown to have target specificity. The case of SART and TRAS endonucleases is particularly illustrative since their respective endonucleases show specificity for the reverse target site, giving the reason for their palindromic name [ 32 , 45 , 56 ] (see Figure 3 ).…”

Section: Telomere Transpositionmentioning

confidence: 99%

“…PLE are a new class of retroelements described a few years ago with some features shared with Group I of introns [ 63 ]. Canonical PLEs are defined by being three to four kilobases in length, and framed by terminal repeats that can be either direct or inverted, called pLTRs [ 56 ]. The first PLEs described contained an endonuclease domain, the GIY-YIG, which was different from the one seen in non-LTR and LTR retrotransposons, and in common with Group I introns [ 64 ].…”

Section: Telomere Transpositionmentioning

confidence: 99%

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Drosophila: Retrotransposons Making up Telomeres

Casacuberta

2017

Viruses

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Drosophila and extant species are the best-studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing Transposon (HeT-A) and Telomere Associated Retrotransposon (TART) with sporadic additions of Telomere Associated and HeT-A Related (TAHRE), all three specialized non-Long Terminal Repeat (non-LTR) retrotransposons. These three very special retroelements transpose in head to tail arrays, always in the same orientation at the end of the chromosomes but never in interior locations. Apparently, retrotransposon and telomerase telomeres might seem very different, but a detailed view of their mechanisms reveals similarities explaining how the loss of telomerase in a Drosophila ancestor could successfully have been replaced by the telomere retrotransposons. In this review, we will discover that although HeT-A, TART, and TAHRE are still the only examples to date where their targeted transposition is perfectly tamed into the telomere biology of Drosophila, there are other examples of retrotransposons that manage to successfully integrate inside and at the end of telomeres. Because the aim of this special issue is viral integration at telomeres, understanding the base of the telomerase exceptions will help to obtain clues on similar strategies that mobile elements and viruses could have acquired in order to ensure their survival in the host genome.

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“…The biological roles of these genomic HHRs, however, have remained poorly known. Rare minimal variants of the type I HHR ( Figure 1A) have been reported in retrotransposons of the Penelope-like (PLEs) (23) and Terminon (24) families, whereas a few copies of highly conserved HHRs in amniotes seem to play a role in mRNA biogenesis (25). More recently, type III HHRs detected in several flowering plants have been found to be involved in the processing of a novel family of non-autonomous LTR retrotransposons, the so-called retrozymes for retroelement with hammerhead ribozymes ( Figure 1B), which spread through circRNA transposition intermediates of 600-800 nt (26).…”

Section: Introductionmentioning

confidence: 98%

Small circRNAs with self-cleaving ribozymes are frequently expressed in metazoan transcriptomes

Cervera

Peña

2019

Preprint

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Ribozymes are catalytic RNAs present in modern genomes but considered as remnants of a prebiotic RNA world. The paradigmatic hammerhead ribozyme (HHR) is a small self-cleaving motif widespread from bacterial to human genomes. Here, we report that most of the classical type I HHRs frequently found in the genomes of diverse animals are contained within a novel family of non-autonomous non-LTR retrotransposons. These retroelements are expressed as abundant linear and circular RNAs of ~170-400 nt in different animal tissues. In vitro analyses confirm an efficient self-cleavage of the HHRs harboured in invertebrate retrozymes, whereas those in retrozymes of vertebrates, such as the axolotl, require to act as dimeric motifs to reach higher self-cleavage rates. Ligation assays of retrozyme RNAs with a protein ligase versus HHR self-ligation indicate that, most likely, tRNA ligases and not the ribozymes are involved in the step of RNA circularization. Altogether, these results confirm the existence of a new and conserved pathway in animals and, likely, in eukaryotes in general, for the efficient biosynthesis of RNA circles through small ribozymes, which will allow the development of biotechnological tools in the emerging field of circRNAs.

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Giant Reverse Transcriptase-Encoding Transposable Elements at Telomeres

Cited by 34 publications

References 63 publications

Endogenization and excision of human herpesvirus 6 in human genomes

Endogenization and excision of human herpesvirus 6 in human genomes

Drosophila: Retrotransposons Making up Telomeres

Small circRNAs with self-cleaving ribozymes are frequently expressed in metazoan transcriptomes

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