Seminars of Interest

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MCB RNA Faculty Candidate Seminar: Dr. Charles Bou-Nader (Visiting Fellow, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), “RNA structure recognition at the virus-host interface”

Event Type
The School of Molecular and Cellular Biology (HOST: Dr. Hong Jin, Biochemistry)
Charles G. Miller Auditorium, B102 Chemical and Life Sciences Laboratory
Mar 1, 2023   10:00 am  
Dr. Charles Bou-Nader
Cara Day
Originating Calendar
Biochemistry Department Seminars

*** NOTE: Time & Date is Wed, March 1 from 10:00-11:00 AM ***

ABSTRACT:  RNAs adopt complex structures critical for their coding and non-coding functions. Recognition of non-self nucleic acid is a major pathway of innate immunity and the first line of defense to curb the infection. In the constant arms race between viruses and the host, some viruses leverage RNA structures to escape the immune response and to promote infectivity. 

Here I will discuss how HIV-1 hijacks host tRNAs to control the cellular localization of its viral polyprotein, Gag.  Combining X-ray crystallography, NMR, mutational, fluorescence and CLIP-seq analyses we revealed that the ‘elbow’ region of the tRNA is recognized by the N-terminal domain of Gag. tRNA binding to Gag delays anchoring of the viral polyprotein at the plasma membrane to promote optimal infectivity. This work reveals that HIV-1 has evolved an extraordinary dual parasitism of host tRNAs, which are exploited not only as primers of reverse transcription, but also as regulators of Gag protein subcellular localization and, thus, viral particle assembly.

I will also highlight the molecular basis of DNA-RNA hybrid recognition by the S9.6 antibody. This antibody is widely used to map R-loop structures in the genome. Combining biochemistry and structural biology approaches we determined its strong specificity for DNA-RNA hybrids over other types of nucleic acids and uncovered a preference for GC rich sequences. Together, this work not only defines a novel hybrid-recognition strategy but also expands our knowledge of nucleic acid immunogenicity.


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