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SUMMARY:LMB Seminar - Mechanisms of Translational Control: From Viral Hija
 cking to Codon-Dependent mRNA Surveillance - In person only - Takuhiro Ito
 \, RIKEN Center for Integrative Medical Sciences
DTSTART:20250901T100000Z
DTEND:20250901T110000Z
UID:TALK233752@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:In eukaryotic cells\, the translation of mRNA into protein is 
 tightly regulated at multiple levels. In this talk\, I will present two co
 mplementary studies that explore distinct\, yet mechanistically intertwine
 d\, aspects of translational control.\nThe first part focuses on how the H
 epatitis C virus (HCV) internal ribosomal entry site (IRES) manipulates ho
 st translation machinery to drive cap-independent viral protein synthesis.
  Through a series of high-resolution cryo-EM structures\, we reveal how th
 e IRES restructures eukaryotic initiation factor 3 (eIF3)\, with its core 
 subunits being displaced by tight interaction with the IRES while the non-
 core subunits remain positioned on the ribosome. Unexpectedly\, the N-term
 inal domain of the eIF3c subunit interacts with the 60S ribosomal subunit 
 during elongation\, suggesting that eIF3 plays roles beyond initiation\, p
 otentially extending to elongation\, termination\, and ribosome recycling.
 \nIn the second part\, we uncover a novel function of the RNA helicase DHX
 29 in regulating mRNA stability based on codon optimality. Using genome-wi
 de CRISPR screening\, selective ribosome profiling\, and cryo-EM\, we demo
 nstrate that DHX29 binds near the A-site entrance of translating ribosomes
  and senses the decoding efficiency of incoming aminoacyl-tRNAs. This ribo
 somal interaction allows DHX29 to recruit the GIGYF2•4EHP complex\, ther
 eby linking slow translation caused by non-optimal codons to mRNA decay pa
 thways.\nTogether\, these studies highlight how both viral elements and ho
 st RNA-binding proteins reshape the translational landscape—either to hi
 jack the host machinery or to maintain transcriptome integrity—offering 
 new structural and mechanistic insights into translational regulation.
LOCATION:In person in the Max Perutz Lecture Theatre (CB2 0QH) 
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