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X-WR-CALDESC:Events for Center for RNA Biomedicine
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DTSTART;TZID=America/Detroit:20231106T160000
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SUMMARY:RNA Innovation Seminar: Irina Artsimovitch\, Ohio State University
DESCRIPTION:“Locking Rho up”\nIrina Artsimovitch\, Ph.D.\nArts & Sciences Distinguished Professor\nDepartment of Microbiology\nThe Ohio State University \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: Bacterial termination factor Rho co-transcriptionally surveils the nascent RNA and releases damaged and junk transcripts from RNA polymerase. During rapid growth\, Rho maintains the transcriptome health\, but how is Rho activity modulated during dormancy or stress\, conditions prevalent in natural habitats? Rho is a hexameric RNA helicase that adopts active closed-ring and inactive open-ring states\, and the interconversion between these states is thought to be a key checkpoint in Rho control. I will discuss two mechanisms by which ligands that bind at Rho subunit interfaces restrain ring dynamics. The Sm-like Rof protein binds at the extended RNA-binding site of Rho\, occluding its RNA- and RNA polymerase-binding sites and locking the hexamer open.  The stress alarmone (p)ppGpp binds to the ATP-binding site and stabilizes the open ring\, triggering phase separation into inactive higher-order oligomers and extended filaments. These and other anti-termination mechanisms are expected to silence Rho under conditions when unrestrained termination would be lethal. \nKeywords: transcription; termination; Rho helicase; stress response; phase separation
URL:https://rna.umich.edu/events/irina-artsimovitch/
LOCATION:MI
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DTSTART;TZID=America/Detroit:20231120T160000
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SUMMARY:RNA Innovation Seminar: George Lisi\, Brown University
DESCRIPTION:“The Invisible Dance of CRISPR-Cas9 through Molecular Space and Time”\nGeorge Lisi\, Ph.D.\nThomas J. & Alice M. Tisch Assistant Professor\nDepartment of Molecular Biology\, Cell Biology & Biochemistry\nBrown University \n  \nIn-person: BSRB\, ABC seminar rooms / hybrid link \nAbstract: This talk will focus on long-range signaling in CRISPR-Cas9\, a cutting-edge genome editing tool. The transformative potential of Cas9 as a precision therapeutic cannot be realized without an understanding of its interdomain communication and the mitigation of deleterious off-target cleavage\, which is being characterized at the atomic level in the group. A series of vignettes will highlight NMR studies of Cas9 through a “divide-and-conquer” approach using engineered protein constructs and first demonstrate that multi-timescale motions in the catalytic nuclease of Cas9 propagates chemical information that regulates cleavage of double-stranded DNA. The talk will also highlight specificity-enhancing mutations in Cas9 that rewire its regulatory mechanism and RNA interactions at the molecular level to mitigate off-target DNA cleavage. Critical energetics of the mechanism will be discussed\, including the importance of metal ions and the protonation state of the catalytic histidine\, studied via catalytic pocket mutations that limit conformational sampling of the Cas9 active state. Lastly\, insight from canonical Cas9s will be expanded to highly stable thermophiles that are more promising for genome engineering and offer tunable high-temperature DNA editing and RNA binding. The underlying chemistry and atomic level dynamics of Cas9 will be linked to its nucleic acid interactions and biological outcomes\, hopefully opening new avenues for intuitive manipulation of its function and precision therapeutic properties.
URL:https://rna.umich.edu/events/george-lisi/
LOCATION:MI
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