siRNA containing a unique 5-nucleotide motif acts as a quencher of IFI16-mediated innate immune response
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved..
We previously reported that some small interfering RNA (siRNA) enhances DNA or DNA virus mediated-interferon (IFN)-λ1(a type III IFN) induction through the crosstalk between retinoic acid-inducible gene I (RIG-I) and interferon gamma-inducible protein 16 (IFI16) signalling pathway. Here we provide further evidence of a new role for siRNA. siRNA containing a 5-nucleotide (nt) motif sequence suppresses DNA-mediated not only type III IFNs, but also type I IFNs and inflammatory cytokines. We define that motif siRNA inhibits the induction when the motif is located at the 3' or 5'-terminus of siRNA. Using THP1-Lucia ISG cells with various DNA stimulants, we reveal that motif siRNA inhibits DNA or DNA virus but not RNA virus-mediated signalling. Motif siRNA specifically interrupts IFI16 but not cyclic GMP-AMP synthase (cGAS) binding to DNA and has 2.5-fold higher affinity to IFI16 than that of siRNA without the motif. We further confirm that motif siRNA potently suppresses HSV-1 virus-mediated IFNs and inflammatory cytokines, such as IFNL1, IFNB and TNFA, in human primary immature dendritic cells. Collectively, these findings may shed light on a novel function of siRNA with the unique 5-nt motif as a quencher of innate immunity and facilitate the development of potential therapeutics to regulate innate immune cascades.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:114 |
|---|---|
| Enthalten in: |
Molecular immunology - 114(2019) vom: 05. Okt., Seite 330-340 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sui, Hongyan [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.01.2020 Date Revised 21.01.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.molimm.2019.08.007 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM300551541 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM300551541 | ||
| 003 | DE-627 | ||
| 005 | 20231225102752.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.molimm.2019.08.007 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1001.xml |
| 035 | |a (DE-627)NLM300551541 | ||
| 035 | |a (NLM)31445477 | ||
| 035 | |a (PII)S0161-5890(19)30382-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sui, Hongyan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a siRNA containing a unique 5-nucleotide motif acts as a quencher of IFI16-mediated innate immune response |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.01.2020 | ||
| 500 | |a Date Revised 21.01.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a We previously reported that some small interfering RNA (siRNA) enhances DNA or DNA virus mediated-interferon (IFN)-λ1(a type III IFN) induction through the crosstalk between retinoic acid-inducible gene I (RIG-I) and interferon gamma-inducible protein 16 (IFI16) signalling pathway. Here we provide further evidence of a new role for siRNA. siRNA containing a 5-nucleotide (nt) motif sequence suppresses DNA-mediated not only type III IFNs, but also type I IFNs and inflammatory cytokines. We define that motif siRNA inhibits the induction when the motif is located at the 3' or 5'-terminus of siRNA. Using THP1-Lucia ISG cells with various DNA stimulants, we reveal that motif siRNA inhibits DNA or DNA virus but not RNA virus-mediated signalling. Motif siRNA specifically interrupts IFI16 but not cyclic GMP-AMP synthase (cGAS) binding to DNA and has 2.5-fold higher affinity to IFI16 than that of siRNA without the motif. We further confirm that motif siRNA potently suppresses HSV-1 virus-mediated IFNs and inflammatory cytokines, such as IFNL1, IFNB and TNFA, in human primary immature dendritic cells. Collectively, these findings may shed light on a novel function of siRNA with the unique 5-nt motif as a quencher of innate immunity and facilitate the development of potential therapeutics to regulate innate immune cascades | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Immunosuppressive motif | |
| 650 | 4 | |a Innate immunity | |
| 650 | 4 | |a Interferon gamma-inducible protein 16 (IFI16) | |
| 650 | 4 | |a siRNA | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a Interferon Type I |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Phosphoproteins |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a IFI16 protein, human |2 NLM | |
| 650 | 7 | |a 148998-64-5 |2 NLM | |
| 650 | 7 | |a DNA |2 NLM | |
| 650 | 7 | |a 9007-49-2 |2 NLM | |
| 700 | 1 | |a Yang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Imamichi, Tomozumi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular immunology |d 1984 |g 114(2019) vom: 05. Okt., Seite 330-340 |w (DE-627)NLM000411434 |x 1872-9142 |7 nnns |
| 773 | 1 | 8 | |g volume:114 |g year:2019 |g day:05 |g month:10 |g pages:330-340 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.molimm.2019.08.007 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 114 |j 2019 |b 05 |c 10 |h 330-340 | ||