Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


E DeLaney Grad Revised.pdf (5.33 MB)

ETD Abstract Container

Abstract Header

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

DeLaney, Elizabeth Erin
http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
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.
Eckhard Jankowsky, Ph.D. (Advisor)
174 p.
Biochemistry
Innate immunity; RIG-I; ATPase

Recommended Citations

Citations

  • DeLaney, E. E. (2014). RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903

    APA Style (7th edition)

  • DeLaney, Elizabeth. RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903.

    MLA Style (8th edition)

  • DeLaney, Elizabeth. "RNA Recognition by the Pattern Recognition Receptor RIG-I: Roles of RNA Binding, Multimerization, and RNA-dependent ATPase Activity." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1405015903

    Chicago Manual of Style (17th edition)

case1405015903
394
© 2014, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.