Nature Microbiology, Journal Year: 2019, Volume and Issue: 4(12), P. 2273 - 2284
Published: Sept. 23, 2019
Language: Английский
Annual Review of Immunology, Journal Year: 2019, Volume and Issue: 37(1), P. 247 - 267
Published: Jan. 11, 2019
Recognition of foreign nucleic acids is the primary mechanism by which a type I interferon-mediated antiviral response triggered. Given that human cells are replete with DNA and RNA, this evolutionary strategy poses an inherent biological challenge, i.e., fundamental requirement to reliably differentiate self-nucleic from nonself acids. We suggest group Mendelian inborn errors immunity referred as interferonopathies relate breakdown self/nonself discrimination, associated mutant genotypes involving molecules playing direct or indirect roles in acid signaling. This perspective begs question sources self-derived drive inappropriate immune response. Resolving will provide insights into tolerance, signaling, complex autoinflammatory disease states. Here we develop these ideas, discussing within broader framework acid-driven inflammation.
Language: Английский
Citations
127
Cell Host & Microbe, Journal Year: 2019, Volume and Issue: 25(6), P. 858 - 872.e13
Published: June 1, 2019
Language: Английский
Citations
114
Mobile DNA, Journal Year: 2019, Volume and Issue: 10(1)
Published: July 26, 2019
Transposable Elements (TEs) are mobile genetic elements whose sequences constitute nearly half of the human genome. Each TE copy can be present in hundreds to thousands locations within genome, complicating and genomic studies these highly repetitive sequences. The recent development better tools for evaluating derived has enabled an increasing appreciation contribution TEs disease. While some have contributed novel beneficial host functions, this review will summarize evidence detrimental activity neurodegenerative disorders. Much pathogenicity implicates endogenous retroviruses (ERVs), a subset that entered genome by retroviral infections germline cells our evolutionary ancestors since been passed down as substantial fraction Human specific ERVs (HERVs) represent youngest thus presumed retain greater function resultant pathogenic potential.
Language: Английский
Citations
109
Viruses, Journal Year: 2020, Volume and Issue: 12(4), P. 382 - 382
Published: March 31, 2020
Deoxynucleoside triphosphate (dNTP) molecules are essential for the replication and maintenance of genomic information in both cells a variety viral pathogens. While process dNTP biosynthesis by cellular enzymes, such as ribonucleotide reductase (RNR) thymidine kinase (TK), has been extensively investigated, negative regulatory mechanism pools was recently found to involve sterile alpha motif (SAM) domain histidine-aspartate (HD) domain-containing protein 1, SAMHD1. When active, triphosphohydrolase activity SAMHD1 degrades dNTPs into their 2'-deoxynucleoside (dN) subparts, steadily depleting intercellular pools. The differential expression levels activation states various cell types contributes unique that either aid (i.e., dividing T cells) or restrict nondividing macrophages) consumes dNTPs. Genetic mutations induce rare inflammatory encephalopathy called Aicardi-Goutières syndrome (AGS), which phenotypically resembles infection. Recent publications have identified diverse roles double-stranded break repair, genome stability, stress response through interferon signaling. Finally, series were also reported cancer while why is mutated these remains investigated. Here, we reviewed studies begun illuminating highly virology, immunology, biology.
Language: Английский
Citations
82
Trends in Genetics, Journal Year: 2023, Volume and Issue: 39(5), P. 381 - 400
Published: March 17, 2023
Language: Английский
Citations
39
Mobile DNA, Journal Year: 2018, Volume and Issue: 9(1)
Published: July 7, 2018
Retrotransposons are transposable elements (TEs) capable of "jumping" in germ, embryonic and tumor cells and, as is now clearly established, the neuronal lineage. Mosaic TE insertions form part a broader landscape somatic genome variation hold significant potential to generate phenotypic diversity, brain elsewhere. At present, LINE-1 (L1) retrotransposon family appears be most active autonomous mammals, based on experimental data obtained from disease-causing L1 mutations, engineered reporter systems tested cultured transgenic rodents, single-cell genomic analyses. However, biological consequences almost all identified thus far remain unknown. In this review, we briefly summarize current state-of-the-art field, including estimates retrotransposition rate neurons. We bring forward hypothesis that an extensive subset retrotransposition-competent L1s may de-repressed mobile soma but largely inactive germline. discuss recent reports non-canonical L1-associated sequence variants propose elevated DNA content reported several neurological disorders predominantly comprise accumulated, unintegrated nucleic acids, rather than insertions. Finally, consider main objectives obstacles going elucidating impact retrotransposition.
Language: Английский
Citations
77
RNA, Journal Year: 2021, Volume and Issue: 27(7), P. 735 - 752
Published: April 22, 2021
Around half of the genomes in mammals are composed transposable elements (TEs) such as DNA transposons and retrotransposons. Several mechanisms have evolved to prevent their activity detrimental impact insertional mutagenesis. Despite these potentially negative effects, TEs essential drivers evolution, certain settings, beneficial hosts. For instance, rewired antiviral gene regulatory network required for early embryonic development. However, due structural similarities between TE-derived viral nucleic acids, cells can misidentify invading viruses trigger major innate immune pathway, type I interferon (IFN) response. This review will focus on different settings which role TE-mediated IFN activation has been documented, including cancer senescence. Importantly, may also play a causative development complex autoimmune diseases characterized by constitutive activation. All observations suggest presence strong but opposing forces driving coevolution defense. A better biological understanding TE replicative cycle well acid sensing provide insights into how two processes interact help design strategies treat human aberrant expression and/or
Language: Английский
Citations
56
Trends in Microbiology, Journal Year: 2018, Volume and Issue: 27(3), P. 254 - 267
Published: Oct. 15, 2018
Language: Английский
Citations
50
Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)
Published: Feb. 2, 2021
Abstract SAMHD1 impedes infection of myeloid cells and resting T lymphocytes by retroviruses, the enzymatic activity protein—dephosphorylation deoxynucleotide triphosphates (dNTPs)—implicates dNTP depletion in innate antiviral immunity. Here we show that allosteric binding sites enzyme are plastic can accommodate oligonucleotides place activators, GTP dNTP. displays a preference for containing phosphorothioate bonds Rp configuration located 3’ to G nucleotides (GpsN), modification pattern occurs mechanism defense prokaryotes. In presence dNTPs, GpsN-containing promotes formation distinct tetramer with mixed occupancy sites. Mutations impair mixed-occupancy complex abolish antiretroviral SAMHD1, but not its ability deplete dNTPs. The findings link nucleic acid shed light on immunomodulatory effects synthetic phosphorothioated raise questions about role phosphorothioation human
Language: Английский
Citations
37
Genes, Journal Year: 2021, Volume and Issue: 12(10), P. 1562 - 1562
Published: Sept. 30, 2021
LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues the organism. The activity L1 retrotransposons strictly controlled by many factors and germ cells at all stages ontogenesis. Alteration was noted number diseases: neuropsychiatric autoimmune diseases, as well forms cancer. Altered for some pathologies associated with epigenetic changes defects genes involved their repression. This review discusses molecular mechanisms retrotransposition regulation elements. contribution controlling expression distribution genome occurs retrotransposition. transcriptional, post-transcriptional integration into described detail. Finally, this also focuses on evolutionary aspects accumulation interplay host system.
Language: Английский
Citations
35