RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity

RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity

Bibliographic Details
Main Author: DeLaney, Elizabeth Erin
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2014
Subjects:
Biochemistry
Innate immunity
RIG-I
ATPase
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case14050159032021-08-03T06:25:46Z RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity DeLaney, Elizabeth Erin Biochemistry Innate immunity RIG-I ATPase Recognition of viral RNA by mammalian cells is critical for the activation of the innate immune system. Viral RNA is recognized by several pathogen recognition receptors, including retinoic acid inducible gene I, or RIG-I. RIG-I consists of two N-terminal tandem caspase activation and recruitment domains, a central helicase/ATPase domain, and a C-terminal regulatory domain. Following RNA binding, RIG-I undergoes a conformational change, ubiquitination, and dimerization, all of which are necessary for interaction with the adaptor protein mitochondrial antiviral signaling (MAVS). Binding to MAVS triggers signaling cascades that induce the transcription of antiviral peptides. RIG-I has been shown to be activated by both dsRNA and dsRNA containing 5’-triphosphates in vivo, and its ATPase activity is critical for activation. A significant body of work has been published regarding the cellular role of RIG-I, but how RIG-I distinguishes viral RNAs from cellular RNAs remains unclear. To understand how RIG-I distinguishes between different substrates, we performed a biochemical analysis of RIG-I RNA binding, ATPase activity, and oligomerization. We used purified RIG-I to quantitatively analyze how RIG-I interacts with various model RNAs. We show that RIG-I binds tightly to dsRNA regardless of the presence of a 5’- triphosphate. Dissociation of RIG-I from RNA is enhanced by ATP. RIG-I ATPase activity is stimulated by RNA duplexes as short as 10 bp, and a RIG-I monomer is sufficient for ATPase activity. RIG-I binds to RNA duplexes with and without blunt ends, however ATPase activity is only activated by RNA duplexes containing at least one blunt end. Collectively, these data suggest that duplex structure and nucleotide binding play a critical role in RIG-I binding and activation. Our data suggest a model in which distinguishing self from non-self RNA requires the recognition of multiple features in a single RNA by RIG-I. 2014-09-02 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903 http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biochemistry
Innate immunity
RIG-I
ATPase
spellingShingle Biochemistry
Innate immunity
RIG-I
ATPase
DeLaney, Elizabeth Erin
RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity
author DeLaney, Elizabeth Erin
author_facet DeLaney, Elizabeth Erin
author_sort DeLaney, Elizabeth Erin
title RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity
title_short RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity
title_full RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity
title_fullStr RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity
title_full_unstemmed RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity
title_sort rna recognition by the pattern recognition receptor rig-i: roles of rna binding, multimerization, and rna-dependent atpase activity
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2014
url http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903
work_keys_str_mv AT delaneyelizabetherin rnarecognitionbythepatternrecognitionreceptorrigirolesofrnabindingmultimerizationandrnadependentatpaseactivity
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