scholarly journals Na dobre i na złe: rola endogennych retroelementów u człowieka

2019 ◽  
Vol 65 (3) ◽  
pp. 217-223
Author(s):  
Małgorzata Zawadzka ◽  
Katarzyna Pachulska-Wieczorek

Elementy transpozycyjne (ang. Transposable Elements, TEs), czyli sekwencje zdolne do sa­modzielnego przemieszczania się w obrębie genomu, odnajdywane są u niemal wszyst­kich organizmów. U człowieka TEs budują prawie połowę genomu i chociaż w większości utraciły zdolność do mobilności, to odegrały znaczącą rolę w ewolucji i zachowaniu pla­styczności genomu. Rozwój w dziedzinach sekwencjonowania i badań funkcjonalnych, przyczynił się do pozyskania coraz większej ilości informacji, wskazujących na ważną rolę zaadaptowanych w genomie ruchomych elementów genetycznych – ich sekwencji re­gulatorowych oraz kodowanych przez nie RNA i białek, w prawidłowym funkcjonowaniu komórek i całego organizmu człowieka. Z drugiej strony część z nich została powiązana z występowaniem chorób głównie o podłożu autoimmunologicznym, w tym neurodegenera­cyjnych oraz nowotworowych. W niniejszym artykule skupiamy się na retroelementach LTR i podsumowujemy stan aktualnej wiedzy na temat pozytywnej i negatywnej roli endogen­nych retrowirusów (ang. Endogenous Retroviruses, ERVs) i retrotranspozonów Ty3/Gypsy na funkcjonowanie organizmu człowieka.

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1089 ◽  
Author(s):  
Rocio Enriquez-Gasca ◽  
Poppy A. Gould ◽  
Helen M. Rowe

The human genome has been under selective pressure to evolve in response to emerging pathogens and other environmental challenges. Genome evolution includes the acquisition of new genes or new isoforms of genes and changes to gene expression patterns. One source of genome innovation is from transposable elements (TEs), which carry their own promoters, enhancers and open reading frames and can act as ‘controlling elements’ for our own genes. TEs include LINE-1 elements, which can retrotranspose intracellularly and endogenous retroviruses (ERVs) that represent remnants of past retroviral germline infections. Although once pathogens, ERVs also represent an enticing source of incoming genetic material that the host can then repurpose. ERVs and other TEs have coevolved with host genes for millions of years, which has allowed them to become embedded within essential gene expression programmes. Intriguingly, these host genes are often subject to the same epigenetic control mechanisms that evolved to combat the TEs that now regulate them. Here, we illustrate the breadth of host gene regulation through TEs by focusing on examples of young (The New), ancient (The Old), and disease-causing (The Ugly) TE integrants.


2017 ◽  
Vol 27 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Muhammad Imran Qadir ◽  
Muhammad Usman ◽  
Muhammad Sajid Hamid Akash

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yu Huining Sun ◽  
Li Huitong Xie ◽  
Xiaoyu Zhuo ◽  
Qiang Chen ◽  
Dalia Ghoneim ◽  
...  

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away. We observed de novo piRNA birth as host responds to a recent retroviral invasion. Avian leukosis virus (ALV) has endogenized prior to chicken domestication, remains infectious, and threatens poultry industry. Domestic fowl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant. This proviral locus does not produce piRNAs in undomesticated wild chickens. Our findings uncover rapid piRNA evolution reflecting contemporary TE activity, identify a new piRNA acquisition modality by activating a pre-existing genomic locus, and extend piRNA defense roles to include the period when endogenous retroviruses are still infectious.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohamed Helmy ◽  
Kumar Selvarajoo

The majority of human genome are non-coding genes. Recent research have revealed that about half of these genome sequences make up of transposable elements (TEs). A branch of these belong to the endogenous retroviruses (ERVs), which are germline viral infection that occurred over millions of years ago. They are generally harmless as evolutionary mutations have made them unable to produce viral agents and are mostly epigenetically silenced. Nevertheless, ERVs are able to express by still unknown mechanisms and recent evidences have shown links between ERVs and major proinflammatory diseases and cancers. The major challenge is to elucidate a detailed mechanistic understanding between them, so that novel therapeutic approaches can be explored. Here, we provide a brief overview of TEs, human ERVs and their links to microbiome, innate immune response, proinflammatory diseases and cancer. Finally, we recommend the employment of systems biology approaches for future HERV research.


2019 ◽  
Author(s):  
Sylvia E. J. Fischer ◽  
Gary Ruvkun

ABSTRACTEndogenous retroviruses and LTR retrotransposons are mobile genetic elements that are closely related to retroviruses. Desilenced endogenous retroviruses are associated with human autoimmune disorders and neurodegenerative diseases. C. elegans and related Caenorhabdites contain LTR retrotransposons and, as described here, numerous integrated viral genes including viral envelope genes that are part of LTR retrotransposons. We found that both LTR retrotransposons and endogenous viral elements are silenced by ADARs (adenosine deaminases acting on double-stranded RNA (dsRNA)) together with the endogenous RNAi factor ERI-6/7, a homolog of Mov10 helicase, a retrotransposon and retrovirus restriction factor in human. siRNAs corresponding to integrated viral genes and LTR retrotransposons, but not to DNA transposons, are dependent on the ADARs and ERI-6/7; on the contrary, siRNAs corresponding to palindromic repeats are increased in adar-eri mutants because of an antiviral RNAi response to dsRNA. Silencing of LTR retrotransposons is dependent on downstream RNAi factors and P granule components but is independent of the viral sensor DRH-1/RIG-I and the nuclear Argonaute NRDE-3. The activation of retrotransposons in the ADAR- and ERI-6/7/MOV10-defective mutant is associated with the induction of the Unfolded Protein Response (UPR), a common response to viral infection. The overlap between genes induced upon viral infection and infection with intracellular pathogens, and genes co-expressed with retrotransposons, suggests that there is a common response to different types of foreign elements that includes a response to proteotoxicity presumably caused by the burden of replicating pathogens and expressed retrotransposons.SIGNIFICANCESilencing of transposable elements and viruses is critical for the maintenance of genome integrity, cellular homeostasis and organismal health. Here we describe multiple factors that control different types of transposable elements, providing insight into how they are regulated. We also identify stress response pathways that are triggered upon mis-regulation of these transposable elements. The conservation of these factors and pathways in human suggests that our studies in C. elegans can provide general insight into the regulation of and response to transposable elements and viruses.


2021 ◽  
Author(s):  
Stylianos Bakoulis ◽  
Robert Krautz ◽  
Nicolas Alcaraz ◽  
Marco Salvatore ◽  
Robin Andersson

Transcription factor binding to regulatory elements is the key process underlying gene regulation during cellular differentiation. Although the specific regulation of genes by transcription factors is generally conserved, regulatory elements themselves are associated with high evolutionary turnover, a process that has been attributed to transposable elements. However, it is unclear how frequent co-option of transposable elements into regulatory elements is and to which regulatory programs they contribute. Here, we report an in-depth characterization of the transposon-derived regulatory landscape of mouse embryonic stem cells. We demonstrate that a substantial number of endogenous retroviral elements are divergently transcribed into unstable RNAs, and that these elements contribute to a sizable proportion of active enhancers and gene promoters. We further show that transposon subfamilies contribute to specific regulatory programs through their enrichment of binding sites for transcription factors, shedding light on the formation of regulatory programs and the origins of regulatory elements.


2020 ◽  
Author(s):  
Wanqing Shao ◽  
Ting Wang

AbstractTransposable elements (TEs) are an integral part of the host transcriptome. TE-containing noncoding RNAs (ncRNAs) exhibit considerable tissue specificity and play crucial roles during development, including stem cell maintenance and cell differentiation. Recent advances in single cell RNA-seq (scRNA-seq) revolutionized cell-type specific gene expression analysis. However, scRNA-seq quantification tools tailored for TEs are lacking, limiting our ability to dissect TE expression dynamics at single cell resolution. To address this issue, we established a TE expression quantification pipeline that is compatible with scRNA-seq data generated across multiple technology platforms. We constructed TE containing ncRNA references using bulk RNA-seq data and demonstrated that quantifying TE expression at the transcript level effectively reduces noise. As proof of principle, we applied this strategy to mouse embryonic stem cells and successfully captured the expression profile of endogenous retroviruses in single cells. We further expanded our analysis to scRNA-seq data from early stages of mouse embryogenesis. Our results illustrated the dynamic TE expression at pre-implantation stages and revealed 137 TE-containing ncRNA transcripts with substantial tissue specificity during gastrulation and early organogenesis.


2021 ◽  
Author(s):  
Ni-Chen Chang ◽  
Quirze Rovira ◽  
Jonathan N Wells ◽  
Cédric Feschotte ◽  
Juan M Vaquerizas

There is considerable interest in understanding the effect of transposable elements (TEs) on embryonic development. Studies in humans and mice are limited by the difficulty of working with mammalian embryos, and by the relative scarcity of active TEs in these organisms. Zebrafish is an outstanding model for the study of vertebrate development and over half of its genome consists of diverse TEs. However, zebrafish TEs remain poorly characterized. Here we describe the demography and genomic distribution of zebrafish TEs and their expression throughout embryogenesis using bulk and single-cell RNA sequencing data. These results reveal a highly dynamic genomic ecosystem comprising nearly 2,000 distinct TE families, which vary in copy number by four orders of magnitude and span a wide range of ages. Longer retroelements tend to be retained in intergenic regions, whilst short interspersed nuclear elements (SINEs) and DNA transposons are more frequently found nearby or within genes. Locus-specific mapping of TE expression reveals extensive TE transcription during development. While two thirds of TE transcripts are likely driven by nearby gene promoters, we still observe stage and tissue-specific expression patterns in self-regulated TEs. Long terminal repeat (LTR) retroelements are most transcriptionally active immediately following zygotic genome activation, whereas DNA transposons are enriched amongst transcripts expressed in later stages of development. Single-cell analysis reveals several endogenous retroviruses expressed in specific somatic cell lineages. Overall, our study provides an important resource for using zebrafish as a model to study the impact of TEs on vertebrate development.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mohanad A. Ibrahim ◽  
Badr M. Al-Shomrani ◽  
Mathew Simenc ◽  
Sultan N. Alharbi ◽  
Fahad H. Alqahtani ◽  
...  

Abstract Background Transposable elements (TEs) are common features in eukaryotic genomes that are known to affect genome evolution critically and to play roles in gene regulation. Vertebrate genomes are dominated by TEs, which can reach copy numbers in the hundreds of thousands. To date, details regarding the presence and characteristics of TEs in camelid genomes have not been made available. Results We conducted a genome-wide comparative analysis of camelid TEs, focusing on the identification of TEs and elucidation of transposition histories in four species: Camelus dromedarius, C. bactrianus, C. ferus, and Vicugna pacos. Our TE library was created using both de novo structure-based and homology-based searching strategies (https://github.com/kacst-bioinfo-lab/TE_ideintification_pipeline). Annotation results indicated a similar proportion of each genomes comprising TEs (35–36%). Class I LTR retrotransposons comprised 16–20% of genomes, and mostly consisted of the endogenous retroviruses (ERVs) groups ERVL, ERVL-MaLR, ERV_classI, and ERV_classII. Non-LTR elements comprised about 12% of genomes and consisted of SINEs (MIRs) and the LINE superfamilies LINE1, LINE2, L3/CR1, and RTE clades. Least represented were the Class II DNA transposons (2%), consisting of hAT-Charlie, TcMar-Tigger, and Helitron elements and comprising about 1–2% of each genome. Conclusions The findings of the present study revealed that the distribution of transposable elements across camelid genomes is approximately similar. This investigation presents a characterization of TE content in four camelid to contribute to developing a better understanding of camelid genome architecture and evolution.


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