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Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00109412" target="_blank" >RIV/00216224:14740/19:00109412 - isvavai.cz</a>

  • Result on the web

    <a href="http://dx.doi.org/10.1261/rna.069625.118" target="_blank" >http://dx.doi.org/10.1261/rna.069625.118</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1261/rna.069625.118" target="_blank" >10.1261/rna.069625.118</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Activation of innate immunity by mitochondrial dsRNA in mouse cells lacking p53 protein

  • Original language description

    Viral and cellular double-stranded RNA (dsRNA) is recognized by cytosolic innate immune sensors, including RIG-I-like receptors. Some cytoplasmic dsRNA is commonly present in cells, and one source is mitochondrial dsRNA, which results from bidirectional transcription of mitochondrial DNA (mtDNA). Here we demonstrate that Trp53 mutant mouse embryonic fibroblasts contain immune-stimulating endogenous dsRNA of mitochondrial origin. We show that the immune response induced by this dsRNA is mediated via RIG-I-like receptors and leads to the expression of type I interferon and proinflammatory cytokine genes. The mitochondrial dsRNA is cleaved by RNase L, which cleaves all cellular RNA including mitochondrial mRNAs, increasing activation of RIG-I-like receptors. When mitochondrial transcription is interrupted there is a subsequent decrease in this immune-stimulatory dsRNA. Our results reveal that the role of p53 in innate immunity is even more versatile and complex than previously anticipated. Our study, therefore, sheds new light on the role of endogenous RNA in diseases featuring aberrant immune responses.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/LM2015091" target="_blank" >LM2015091: National Center for Medical Genomic</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2019

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    RNA

  • ISSN

    1355-8382

  • e-ISSN

    1469-9001

  • Volume of the periodical

    25

  • Issue of the periodical within the volume

    6

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    14

  • Pages from-to

    713-726

  • UT code for WoS article

    000468092200005

  • EID of the result in the Scopus database

    2-s2.0-85066118492