title: Rig-I regulates NF-κB activity through binding to Nf-κb1 3'-UTR mRNA.
abstract: Retinoic acid inducible gene I (RIG-I) senses viral RNAs and triggers innate antiviral responses through induction of type I IFNs and inflammatory cytokines. However, whether RIG-I interacts with host cellular RNA remains undetermined. Here we report that Rig-I interacts with multiple cellular mRNAs, especially Nf-κb1. Rig-I is required for NF-κB activity via regulating Nf-κb1 expression at posttranscriptional levels. It interacts with the multiple binding sites within 3'-UTR of Nf-κb1 mRNA. Further analyses reveal that three distinct tandem motifs enriched in the 3'-UTR fragments can be recognized by Rig-I. The 3'-UTR binding with Rig-I plays a critical role in normal translation of Nf-κb1 by recruiting the ribosomal proteins [ribosomal protein L13 (Rpl13) and Rpl8] and rRNAs (18S and 28S). Down-regulation of Rig-I or Rpl13 significantly reduces Nf-κb1 and 3'-UTR-mediated luciferase expression levels. These findings indicate that Rig-I functions as a positive regulator for NF-κB signaling and is involved in multiple biological processes in addition to host antivirus immunity.
authors.affiliation: State Key Laboratory of Medical Genomics, Research Center for Experimental Medicine, Shanghai Institute of Hematology, Rui-Jin Hospital- Shanghai Jiao Tong University School of Medicine, SJTUSM, Shanghai 200025, China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Zhang
authors.forename: Zi-Xing
authors.initials: ZX
authors.lastname: Liu
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Sun
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Shun-Yuan
authors.initials: SY
authors.lastname: Lu
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Liu
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Huang
authors.forename: Yin-Yin
authors.initials: YY
authors.lastname: Xie
authors.forename: Hou-Bao
authors.initials: HB
authors.lastname: Zhu
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Dang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Zheng
authors.forename: Yi-Xue
authors.initials: YX
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhu-Gang
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D047468:Immunoprecipitation; D008156:Luciferases; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D056004:Molecular Dynamics Simulation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D016328:NF-kappa B; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C520792:Rpl13a protein, mouse; C075184:ribosomal protein L8, rat; D008156:Luciferases; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
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