BEGIN:VCALENDAR VERSION:2.0 PRODID:-//wp-events-plugin.com//7.2.2.1//EN TZID:Asia/Jerusalem X-WR-TIMEZONE:Asia/Jerusalem BEGIN:VEVENT UID:1160@biology.technion.ac.il DTSTART;TZID=Asia/Jerusalem:20230215T133000 DTEND;TZID=Asia/Jerusalem:20230215T140000 DTSTAMP:20230131T080213Z URL:https://biology.technion.ac.il/en/seminars/msc-graduate-seminar-hila-b en-arie-zilberman/ SUMMARY:MSc Graduate Seminar- Hila Ben-arie Zilberman [No Categories] DESCRIPTION:Location: hybrid- in the Faculty Auditorium/ZOOM: https://techn ion.zoom.us/j/6141638094 Hila Ben-arie Zilberman\n Affiliation: \n Host: Dr. Shiber Ayala\n  \;\n\nISG15 and ISGylation at the ribosome: mecha nistic analysis\, innate immune response\, and impact on translation\n\n&n bsp\;\n\nThe innate immune response is the first line of defense against a ll pathogens. The response incorporates the secretion of cytokines like ty pe I interferons (IFN-I). There are hundreds of interferon-stimulated gene s (ISGs)\, with ISG15 being one of the primary ones. ISG15 is a ubiquitin -like protein\, which rapidly modifies a vast array of cellular and viral targets via a mechanism known as ISGylation. Like ubiquitination\, ISGylat ion is mediated via an E1-E2-E3 enzymatic cascade. The main ISG15-E3 ligas e has been associated with translating ribosomes\, suggesting ISG15 prefer ably modifies newly synthesized proteins. Yet\, their effects on the cellu lar translatome\, protein turnover\, and feedback to the transcriptome rem ain largely unknown. Here we provide structural modeling analysis of the k nown ISG15 ligases: HERC5\, HHARI\, and TRIM25. This revealed putative ISG 15 and substrate interaction sites\, as well as putative binding sites nea r the ribosome exit tunnel. Analyzing HeLa-/-isg15 deletion cells by polys ome profiling\, we found a cellular translation inhibition phenotype. Thes e cells display lower translation levels\, with and without interferon tre atment. This is in stark contrast to WT HeLa cells\, displaying inhibition of translation\, only following IFN treatment. Transfection of HeLa-/-isg 15  cells with an IFN-induced vector carrying ISG15 rescued the translati on inhibition phenotype. Next\, we will perform proteomics and mRNA analys is of translating ribosomes purified from HeLa\, HeLa-/-isg15\, and U2OS c ells\, with and without IFN treatment. This will provide mechanistic insig ht into ISG15 and ribosomal function during infection.\n\n \;\n\nWill be in English LOCATION:hybrid- in the Faculty Auditorium/ZOOM: https://technion.zoom.us/j /6141638094 END:VEVENT BEGIN:VTIMEZONE TZID:Asia/Jerusalem X-LIC-LOCATION:Asia/Jerusalem BEGIN:STANDARD DTSTART:20221030T010000 TZOFFSETFROM:+0300 TZOFFSETTO:+0200 TZNAME:IST END:STANDARD END:VTIMEZONE END:VCALENDAR