Structural features of influenza A virus panhandle RNA enabling the activation of RIG-I independently of 5'-triphosphate.
Retinoic acid-inducible gene I (RIG-I) recognizes specific molecular patterns of viral RNAs for inducing type I interferon. The C-terminal domain (CTD) of RIG-I binds to double-stranded RNA (dsRNA) with the 5'-triphosphate (5'-PPP), which induces a conformational change in RIG-I to an active form. It has been suggested that RIG-I detects infection of influenza A virus by recognizing the 5'-triphosphorylated panhandle structure of the viral RNA genome. Influenza panhandle RNA has a unique structure with a sharp helical bending. In spite of extensive studies of how viral RNAs activate RIG-I, whether the structural elements of the influenza panhandle RNA confer the ability to activate RIG-I signaling has been poorly explored. Here, we investigated the dynamics of the influenza panhandle RNA in complex with RIG-I CTD using NMR spectroscopy and showed that the bending structure of the panhandle RNA negates the requirement of a 5'-PPP moiety for RIG-I activation.
Department of Chemistry, KAIST, Daejeon 34141, Republic of Korea Disease Target Structure Research Center, KRIBB, Daejeon 34141, Republic of Korea.
Mi-Kyung
MK
Lee
Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju, Gyeongnam 52828, Republic of Korea.
Hee-Eun
HE
Kim
Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
Eun-Byeol
EB
Park
Department of Chemistry, KAIST, Daejeon 34141, Republic of Korea.
Janghyun
J
Lee
Department of Chemistry, KAIST, Daejeon 34141, Republic of Korea.
Ki-Hun
KH
Kim
Department of Chemistry, KAIST, Daejeon 34141, Republic of Korea.
Kyungeun
K
Lim
Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.
Seoyun
S
Yum
Department of Chemistry, KAIST, Daejeon 34141, Republic of Korea.
Young-Hoon
YH
Lee
Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea suk-jo.kang@kaist.ac.kr.
Suk-Jo
SJ
Kang
Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju, Gyeongnam 52828, Republic of Korea joonhwa@gnu.ac.kr.
Joon-Hwa
JH
Lee
Department of Chemistry, KAIST, Daejeon 34141, Republic of Korea byongseok.choi@kaist.ac.kr.
Byong-Seok
BS
Choi
D020029:Base Pairing; D002151:Calorimetry; D000071457:DEAD Box Protein 58 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D009980:Influenza A virus / Q000235:genetics*; D016899:Interferon-beta / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D011122:Polyphosphates / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D020871:RNA Stability; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic; D013816:Thermodynamics
D011122:Polyphosphates; D012367:RNA, Viral; D011971:Receptors, Immunologic; D016899:Interferon-beta; D006859:Hydrogen; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; C005692:triphosphoric acid