Type I Interferon Controls Propagation of Long Interspersed Element-1

Yu, Qiujing; Carbone, Christopher J.; Katlinskaya, Yuliya; Zheng, Hui; Zheng, Ke; Luo, Mengcheng; Wang, P. Jeremy; Greenberg, Roger A.; Fuchs, Serge Y.

doi:10.1074/jbc.m114.612374

Cited by 60 publications

(70 citation statements)

References 51 publications

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“…The described interactions between infectious viruses and the transposons that comprise the bulk of mammalian host genomes are consistent with the hypothesis that transposons are symbionts integral to genomic stress responses (McClintock 1984), including antiviral immune responses (Zeng et al 2014;Yu et al 2015). The piRNA system in mammals is known to silence quasi-nonself transposon nucleic acids; our observations raise the hypothesis that, as for CRISPR/Cas in prokaryotes, truly exogenous nonself nucleic acids from infecting viruses can be targeted by piRNA-like RNAs, but that this requires genetic information flow in an unexpected retrotransposon-dependent manner (Nuñez et al 2015).…”

Section: Discussionmentioning

confidence: 51%

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Parrish

Fujino

Shiromoto

et al. 2015

RNA

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Endogenous bornavirus-like nucleoprotein elements (EBLNs) are sequences within vertebrate genomes derived from reverse transcription and integration of ancient bornaviral nucleoprotein mRNA via the host retrotransposon machinery. While species with EBLNs appear relatively resistant to bornaviral disease, the nature of this association is unclear. We hypothesized that EBLNs could give rise to antiviral interfering RNA in the form of PIWI-interacting RNAs (piRNAs), a class of small RNA known to silence transposons but not exogenous viruses. We found that in both rodents and primates, which acquired their EBLNs independently some 25-40 million years ago, EBLNs are present within piRNA-generating regions of the genome far more often than expected by chance alone (P = 8 × 10 −3 -6 × 10 −8 ). Three of the seven human EBLNs fall within annotated piRNA clusters and two marmoset EBLNs give rise to bona fide piRNAs. In both rats and mice, at least two of the five EBLNs give rise to abundant piRNAs in the male gonad. While no EBLNs are syntenic between rodent and primate, some of the piRNA clusters containing EBLNs are; thus we deduce that EBLNs were integrated into existing piRNA clusters. All true piRNAs derived from EBLNs are antisense relative to the proposed ancient bornaviral nucleoprotein mRNA. These observations are consistent with a role for EBLN-derived piRNA-like RNAs in interfering with ancient bornaviral infection. They raise the hypothesis that retrotransposon-dependent virus-to-host gene flow could engender RNA-mediated, sequence-specific antiviral immune memory in metazoans analogous to the CRISPR/Cas system in prokaryotes.

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Section: Discussionmentioning

confidence: 51%

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Parrish

Fujino

Shiromoto

et al. 2015

RNA

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“…Mechanisms to limit such activity most probably exist, which may include RNA interference, changes to the methylation status of DNA, histone modifications and a retroelement-induced type I IFN response 66 . It is possible that TREX1, RNase H2, SAMHD1 and ADAR might all have a role in the metabolism of retroelements, whereas IFIH1 may be 'set' to limit its affinity for, or response to, baseline levels of endogenous, possibly retroelement-derived, dsRNA.…”

Section: Retroelements and Dna Damage In Agsmentioning

confidence: 99%

Aicardi–Goutières syndrome and the type I interferonopathies

2015

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Dissection of the genetic basis of Aicardi-Goutières syndrome has highlighted a fundamental link between nucleic acid metabolism, innate immune sensors and type I interferon induction. This had led to the concept of the human interferonopathies as a broader set of Mendelian disorders in which a constitutive upregulation of type I interferon activity directly relates to disease pathology. Here, we discuss the molecular and cellular basis of the interferonopathies, their categorization, future treatment strategies and the insights they provide into normal physiology.

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“…These mutations may result in inappropriate accumulation of nucleic acids and subsequent activation of RNA and DNA sensors such as MDA5 and cGAS [68] [69]. In the mouse, artificial activation of Long Interspersed Element-1 (LINE-1) has been shown to increase the expression of IFN-I and ISGs [70]. Interestingly, silenced endogenous sequences can be activated by innate immune responses, suggesting a role for these sequences in signal amplification.…”

Section: Reactivation Of Transposable Elements Is Triggered and Sensementioning

confidence: 99%

Sequence-Specific Sensing of Nucleic Acids

Vabret

Bhardwaj

Greenbaum

2017

Trends in Immunology

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Innate immune cells are endowed with many nucleic acid receptors, but the role of sequence in the detection of foreign organisms remains unclear. Can sequence patterns influence recognition? And how can we infer those patterns from sequence data? Here, we detail recent computational and experimental evidence associated with sequence-specific sensing. We review the mechanisms underlying the detection and discrimination of foreign sequences from self. We also describe quantitative approaches used to infer the stimulatory capacity of a given pathogen nucleic acid species, and the influence of sequence-specific sensing on host-pathogen coevolution, including endogenous sequences of foreign origin. Finally, we speculate how further studies of sequence-specific sensing will be useful to improve vaccine design, gene therapy and cancer treatment.

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Type I Interferon Controls Propagation of Long Interspersed Element-1

Cited by 60 publications

References 51 publications

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

piRNAs derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals

Aicardi–Goutières syndrome and the type I interferonopathies

Sequence-Specific Sensing of Nucleic Acids

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