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10.1261/rna.078923.121

http://scihub22266oqcxt.onion/10.1261/rna.078923.121
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34315815!8522697!34315815
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suck abstract from ncbi


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pmid34315815      RNA 2021 ; 27 (11): 1318-1329
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  • SARS-CoV-2 infection triggers widespread host mRNA decay leading to an mRNA export block #MMPMID34315815
  • Burke JM; St Clair LA; Perera R; Parker R
  • RNA 2021[Nov]; 27 (11): 1318-1329 PMID34315815show ga
  • The transcriptional induction of interferon (IFN) genes is a key feature of the mammalian antiviral response that limits viral replication and dissemination. A hallmark of severe COVID-19 disease caused by SARS-CoV-2 is the low presence of IFN proteins in patient serum despite elevated levels of IFN-encoding mRNAs, indicative of post-transcriptional inhibition of IFN protein production. Here, we performed single-molecule RNA visualization to examine the expression and localization of host mRNAs during SARS-CoV-2 infection. Our data show that the biogenesis of type I and type III IFN mRNAs is inhibited at multiple steps during SARS-CoV-2 infection. First, translocation of the interferon regulatory factor 3 (IRF3) transcription factor to the nucleus is limited in response to SARS-CoV-2, indicating that SARS-CoV-2 inhibits RLR-MAVS signaling and thus weakens transcriptional induction of IFN genes. Second, we observed that IFN mRNAs primarily localize to the site of transcription in most SARS-CoV-2 infected cells, suggesting that SARS-CoV-2 either inhibits the release of IFN mRNAs from their sites of transcription and/or triggers decay of IFN mRNAs in the nucleus upon exiting the site of transcription. Lastly, nuclear-cytoplasmic transport of IFN mRNAs is inhibited during SARS-CoV-2 infection, which we propose is a consequence of widespread degradation of host cytoplasmic basal mRNAs in the early stages of SARS-CoV-2 replication by the SARS-CoV-2 Nsp1 protein, as well as the host antiviral endoribonuclease, RNase L. Importantly, IFN mRNAs can escape SARS-CoV-2-mediated degradation if they reach the cytoplasm, making rescue of mRNA export a viable means for promoting the immune response to SARS-CoV-2.
  • |*RNA Stability[MESH]
  • |A549 Cells[MESH]
  • |Angiotensin-Converting Enzyme 2/genetics/metabolism[MESH]
  • |COVID-19/*genetics/virology[MESH]
  • |Cell Line[MESH]
  • |Endoribonucleases/genetics/metabolism[MESH]
  • |Host-Pathogen Interactions/*genetics[MESH]
  • |Humans[MESH]
  • |In Situ Hybridization, Fluorescence/methods[MESH]
  • |Interferon Regulatory Factor-3/genetics/metabolism[MESH]
  • |Interferons/*genetics/metabolism[MESH]
  • |RNA, Messenger/metabolism[MESH]
  • |SARS-CoV-2/*pathogenicity[MESH]
  • |Single Molecule Imaging[MESH]


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