“…Another in an increasingly long line supportive of this notion is a recent report that inborn errors in RNA polymerase III was associated with and caused severe disease, including pneumonia and encephalitis in 4 children with varicella zoster virus infection [4].…”
“…Another in an increasingly long line supportive of this notion is a recent report that inborn errors in RNA polymerase III was associated with and caused severe disease, including pneumonia and encephalitis in 4 children with varicella zoster virus infection [4].…”
“…Another study demonstrated that during infection with invertebrate iridescent virus 6 (IIV-6), an insect DNA virus, the mammalian host requires RNA polymerase III to produce IFN-β (Ahlers et al, 2016). Through whole exome sequencing of 21 human patients, a recent study found that different mutations in the RNA polymerase III gene can explain why some patients suffer from severe acute VZV infection (Ogunjimi et al, 2017). In contrast, sequencing of 222 patients suffering from herpesviral encephalitis did not result in identification of RNA polymerase III mutations, which may be explained by the presence of high AT base content in several genome islands of VZV and overall lower cGAS expression in blood cells (Gram et al, 2017; Ogunjimi et al, 2017).…”
Section: Intracellular Recognition Of Dnamentioning
confidence: 99%
“…Through whole exome sequencing of 21 human patients, a recent study found that different mutations in the RNA polymerase III gene can explain why some patients suffer from severe acute VZV infection (Ogunjimi et al, 2017). In contrast, sequencing of 222 patients suffering from herpesviral encephalitis did not result in identification of RNA polymerase III mutations, which may be explained by the presence of high AT base content in several genome islands of VZV and overall lower cGAS expression in blood cells (Gram et al, 2017; Ogunjimi et al, 2017). Together, these studies indicate the important role of RNA polymerase III in mediating an innate immune response to DNA viruses.…”
Section: Intracellular Recognition Of Dnamentioning
Innate immunity, the first line of defense against invading pathogens, is an ancient form of host defense found in all animals, from sponges to humans. During infection, innate immune receptors recognize conserved molecular patterns, such as microbial surface molecules, metabolites produces during infection, or nucleic acids of the microbe’s genome. When initiated, the innate immune response activates a host defense program that leads to the synthesis proteins capable of pathogen killing. In mammals, the induction of cytokines during the innate immune response leads to the recruitment of professional immune cells to the site of infection, leading to an adaptive immune response. While a fully functional innate immune response is crucial for a proper host response and curbing microbial infection, if the innate immune response is dysfunctional and is activated in the absence of infection, autoinflammation and autoimmune disorders can develop. Therefore, it follows that the innate immune response must be tightly controlled to avoid an autoimmune response from host-derived molecules, yet still unencumbered to respond to infection. In this review, we will focus on the innate immune response activated from cytosolic nucleic acids, derived from the microbe or host itself. We will depict how viruses and bacteria activate these nucleic acid sensing pathways and their mechanisms to inhibit the pathways. We will also describe the autoinflammatory and autoimmune disorders that develop when these pathways are hyperactive. Finally, we will discuss gaps in knowledge with regard to innate immune response failure and identify where further research is needed.
“…Additionally, Ogunjimi et al supported that defects in RNA polymerase III subunit A (POLR3A) and POLR3C F I G U R E 4 aaRSs and immune responses. 113 The leucocytes in patients with pathogenic mutations had defective production of IFN after VZV infection and could not effectively inhibit virus replication. 101 B, Apoptotic cells secreted TyrRS, which was cleaved into MiniTyr and EMAP fragments by Mmp.…”
Section: Perspectivementioning
confidence: 99%
“…105 (Continued) increased the susceptibility of healthy children to severe varicella zoster virus (VZV) infection. 113 The leucocytes in patients with pathogenic mutations had defective production of IFN after VZV infection and could not effectively inhibit virus replication. RNA 2',3'-cyclic phosphate and 5'-OH ligase (RTCB), the catalytic subunit of the tRNA ligase complex, together with its cofactor archease mediated X-box binding protein 1 (XBP1) mRNA splicing during the unfolded protein response (UPR).…”
Section: Conclusion and Future Perspectivementioning
Transfer RNA (tRNA), often considered as a housekeeping molecule, mainly participates in protein translation by transporting amino acids to the ribosome. Nevertheless, accumulating evidence has shown that tRNAs are closely related to various physiological and pathological processes. The proper functioning of the immune system is the key to human health. The aim of this review is to investigate the relationships between tRNAs and the immune system. We detail the biogenesis and structure of tRNAs and summarize the pathogen tRNA-mediated infection and host responses. In addition, we address recent advances in different aspects of tRNA-associated dysregulation in immune responses and immune diseases, such as tRNA molecules, tRNA modifications, tRNA derivatives and tRNA aminoacylation. Therefore, tRNAs play an important role in immune regulation. Although our knowledge of tRNAs in the context of immunity remains, for the most part, unknown, this field deserves in-depth research to provide new ideas for the treatment of immune diseases.
K E Y W O R D Sbiogenesis, immune diseases, immune responses, tRNA F I G U R E 1 The biogenesis and structure of tRNAs. tRNA: Transfer RNA; Pol III: RNA polymerase III; pre-tRNA: Precursor tRNA; mRNA: Messenger RNA; aaRS: Aminoacyl-tRNA synthetase; tsRNA: tRNA-derived small RNA; tRF: tRNA-derived fragment; tiRNA: tRNA-derived stress-induced RNA
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