Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation

Lü, Jian; Shao, Wen; Chao, Lei; Yin, Yafei; Li, Tong; Zhang, Hui; Hong, Yantao; Percharde, Michelle; Guo, Lerui; Wu, Zhongyang; Liu, Lichao; Liu, Wei; Pei, Yan; Ramalho-Santos, Miguel; Sun, Yujie; Shen, Xiaohua

doi:10.1016/j.celrep.2020.02.048

Cited by 116 publications

(154 citation statements)

References 90 publications

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“…Abnormally upregulation of retrotransposons cause insertions, deletions and inversions in genome (16,17), resulting in compromised genetic stability and even cell death (18,19). Accumulated evidence in recent years also proved their importance in orchestration of gene expression (20), regulation of chromatin structure (21) and modulation of developmental program (22,23).…”

Section: Expression Of Most Of Retrotransposon Members Is Suppressed mentioning

confidence: 99%

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Yin

Liu

et al. 2020

Preprint

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Abstract Background: There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent particularly dangerous coronaviruses are MERS-CoV, SARS-CoV and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. Results: Here, we go deep into transcriptome of MERS-CoV, SARS-CoV and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression through upregulation of TET genes. Similar upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation will lead to increased genome instability and more frequent readthrough from retrotransposon to dysregulate gene expression. People with higher basal level of retrotransposon like cancer patients and aged people will have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed significant amount of chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA, and this may apply for other coronaviruses. Here we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. Conclusions: In summary, we propose that infection of coronaviruses especially SARS-CoV-2 induce retrotransposon activation, formation of chimeric coronavirus-retrotransposon RNA, and elicits more severe symptoms in patients with underlying diseases. More attention may need to be paid to potential harm contributed by retrotransposon dysregulation in treatment of coronavirus-infected patients.

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Section: Expression Of Most Of Retrotransposon Members Is Suppressed mentioning

confidence: 99%

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Yin

Liu

et al. 2020

Preprint

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“…Recent data show that families of repetitive elements are tightly associated with the expression of particular classes of genes during embryo development and in embryonic stem cells: Alu/SINE sequences tendentially associate with housekeeping genes, while LINE-1-enriched genes have specialized functions [ 83 ]. These data strongly suggest that retrotransposition events provide dynamic molecular ‘tools’ in the build-up of functional genomic circuits.…”

Section: Decoding the Sperm ‘Rna Code’ And The Reprogramming Of Earlymentioning

confidence: 99%

Transgenerational epigenetic reprogramming of early embryos: a mechanistic model

Spadafora

2020

Environmental Epigenetics

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The notion that epigenetic information can be transmitted across generations is supported by mounting waves of data, but the underlying mechanisms remain elusive. Here, a model is proposed which combines different lines of experimental evidence. First, it has been shown that somatic tissues exposed to stressing stimuli release circulating RNA-containing extracellular vesicles; second, epididymal spermatozoa can take up, internalize and deliver the RNA-containing extracellular vesicles to oocytes at fertilization; third, early embryos can process RNA-based information. These elements constitute the building blocks upon which the model is built. The model proposes that a continuous stream of epigenetic information flows from parental somatic tissues to the developing embryos. The flow can cross the Weismann barrier, is mediated by circulating vesicles and epididymal spermatozoa, and has the potential to generate epigenetic traits that are then stably acquired in the offspring. In a broader perspective, it emerges that a natural ‘assembly line’ operates continuously, aiming at passing the parental epigenetic blueprint in growing embryos.

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“…In addition to their epigenetic activity, TEs are active genetically and can alter transcript splicing patterns by becoming exonised into transcripts (Macfarlan et al 2012;Wang et al 2014;Goke et al 2015;Grow et al 2015). TEs make a major contribution to the sequences of long-non-coding RNAs (lncRNAs) (Lev-Maor et al 2008;Kelley and Rinn 2012;Kapusta et al 2013;Naville et al 2016), and whilst lncRNAs have roles in normal biological processes (Goff and Rinn 2015;Bourque et al 2018;Lu et al 2020), and disease (Wapinski and Chang 2011;Carlevaro-Fita et al 2020), the roles of TEs inside the lncRNAs has received less attention. One model suggests that TEs act as functional domains within lncRNAs, something akin to globular domains of proteins (Johnson and Guigo 2014;Chishima et al 2018).…”

Section: Introductionmentioning

confidence: 99%

Transposable Element-Gene Splicing Modulates the Transcriptional Landscape of Human Pluripotent Stem Cells

Babarinde

et al. 2020

Preprint

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Transposable elements (TEs) occupy nearly 50% of mammalian genomes and are both potential dangers to genome stability and functional genetic elements. TEs can be expressed and exonised as part of a transcript, however, their full contribution to the transcript splicing remains unresolved. Here, guided by long and short read sequencing of RNAs, we show that 26% of coding and 65% of non-coding transcripts of human pluripotent stem cells (hPSCs) contain TEs. Different TE families have unique integration patterns with diverse consequences on RNA expression and function. We identify hPSC-specific splicing of endogenous retroviruses (ERVs) as well as LINE L1 elements into protein coding genes that generate TE-derived peptides. Finally, single cell RNA-seq reveals that proliferating hPSCs are dominated by ERV-containing transcripts, and subpopulations express SINE or LINE-containing transcripts. Overall, we demonstrate that TE splicing modulates the pluripotency transcriptome by enhancing and impairing transcript expression and generating novel transcripts and peptides.

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Genomic Repeats Categorize Genes with Distinct Functions for Orchestrated Regulation

Cited by 116 publications

References 90 publications

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Exogenous coronavirus interacts with endogenous retrotransposon in human cells

Transgenerational epigenetic reprogramming of early embryos: a mechanistic model

Transposable Element-Gene Splicing Modulates the Transcriptional Landscape of Human Pluripotent Stem Cells

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