Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation

Carter, Ava C.; Xu, Jin; Nakamoto, Meagan Y; Wei, Yuning; Zarnegar, Brian; Shi, Quanming; Broughton, James P.; Ransom, Ryan C.; Salhotra, Ankit; Nagaraja, Surya; Li, Rui; Dou, Diana R.; Yost, Kathryn E.; Cho, Seung Woo; Mistry, Anil; Longaker, Michael T.; Khavari, Paul A.; Batey, Robert T.; Wuttke, Deborah S.; Chang, Howard Y.

doi:10.7554/elife.54508

Cited by 38 publications

(48 citation statements)

References 59 publications

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“…Also worth noting was that most exFVtgrs contained stop codons and their ORFs were incomplete, which might have indicated that they were likely to be ERV-derived long noncoding RNAs (lncRNAs) rather than exogenous retroviruses. Moreover, they might also function as lncRNAs to participate in genomic regulatory processes (56)(57)(58). However, this speculation should be verified by further study.…”

Section: Discussionmentioning

confidence: 96%

Multiple infiltration and cross-species transmission of foamy viruses across Paleozoic to Cenozoic era

Chen

Zhang

Wei

et al. 2020

Preprint

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Foamy viruses (FVs) are complex retroviruses that can infect humans and other animals. In this study, by integrating transcriptomic and genomic data, we discovered 412 FVs from 6 lineages in amphibians, which significantly increased the known set of FVs in amphibians. Among these lineages, salamander FVs maintained a co-evolutionary pattern with their hosts that could be dated back to the Paleozoic era, while, on the contrary, frog FVs were much more likely acquired from cross-species (class level) transmission in the Cenozoic era. In addition, we found three distinct FV lineages had integrated into the genome of a salamander. Unexpectedly, we identified a potential exogenous form of FV circulated in caecilian, demonstrating the existence of exogenous form of FV besides mammals. Our discovery of rare phenomena in amphibian FVs has overturned our collective understanding of the macroevolution of the complex retrovirus.ImportanceFoamy viruses (FVs) represent, more so than other viruses, the best model of co-evolution between a virus and a host. This study represents so far, the largest investigation of amphibian FVs and revealed 412 FVs of 6 distinct lineages from three major orders of amphibians. Besides co-evolutionary pattern, cross-species and repeated infection were also observed during evolution of amphibian FVs. Remarkably, expressed FVs including a potential exogenous form were discovered, suggesting live FVs could be underestimated in nature. These findings revealed the multiple origin and complex evolution of amphibian FVs started from the Paleozoic era.

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Section: Discussionmentioning

confidence: 96%

Multiple infiltration and cross-species transmission of foamy viruses across Paleozoic to Cenozoic era

Chen

Zhang

Wei

et al. 2020

Preprint

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“…Recently, it has been shown that depletion of Spen reactivates a subset of ERVs in mouse ESCs. Spen has been found to bind to ERV-derived RNA and recruited several chromatin remodeling factors such as histone deacetylases [116]. Another example for RNA-mediated regulation of ERVs is the Piwi-interacting RNA (piRNA) pathway.…”

Section: Rna-mediated Targeting Of Tesmentioning

confidence: 99%

Silencing and Transcriptional Regulation of Endogenous Retroviruses: An Overview

Geis

Goff

2020

Viruses

126

103

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Almost half of the human genome is made up of transposable elements (TEs), and about 8% consists of endogenous retroviruses (ERVs). ERVs are remnants of ancient exogenous retrovirus infections of the germ line. Most TEs are inactive and not detrimental to the host. They are tightly regulated to ensure genomic stability of the host and avoid deregulation of nearby gene loci. Histone-based posttranslational modifications such as H3K9 trimethylation are one of the main silencing mechanisms. Trim28 is one of the identified master regulators of silencing, which recruits most prominently the H3K9 methyltransferase Setdb1, among other factors. Sumoylation and ATP-dependent chromatin remodeling factors seem to contribute to proper localization of Trim28 to ERV sequences and promote Trim28 interaction with Setdb1. Additionally, DNA methylation as well as RNA-mediated targeting of TEs such as piRNA-based silencing play important roles in ERV regulation. Despite the involvement of ERV overexpression in several cancer types, autoimmune diseases, and viral pathologies, ERVs are now also appreciated for their potential positive role in evolution. ERVs can provide new regulatory gene elements or novel binding sites for transcription factors, and ERV gene products can even be repurposed for the benefit of the host.

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“…Finally, it is now possible to successfully create synthetic lncRNAs. By adding RNA shapes to carefully chosen RNA templates, investigators are starting to create designer lncRNAs that can regulate chromatin in vivo 100 , suffice to partly rescue the physiological lncRNA gene knockout 102 , or target RNAs to specific cytotopic locations within the cell 103 , 104 .…”

Section: Long Non-coding Rnas: a Time To Buildmentioning

confidence: 99%

The road ahead in genetics and genomics

et al. 2020

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In celebration of the 20th anniversary of Nature Reviews Genetics , we asked 12 leading researchers to reflect on the key challenges and opportunities faced by the field of genetics and genomics. Keeping their particular research area in mind, they take stock of the current state of play and emphasize the work that remains to be done over the next few years so that, ultimately, the benefits of genetic and genomic research can be felt by everyone.

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Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation

Cited by 38 publications

References 59 publications

Multiple infiltration and cross-species transmission of foamy viruses across Paleozoic to Cenozoic era

Multiple infiltration and cross-species transmission of foamy viruses across Paleozoic to Cenozoic era

Silencing and Transcriptional Regulation of Endogenous Retroviruses: An Overview

The road ahead in genetics and genomics

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