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SUMMARY:The crosstalk between RNA transcription and splicing - Suyang Zhan
 g - MRC LMB
DTSTART:20251113T150000Z
DTEND:20251113T160000Z
UID:TALK235567@talks.cam.ac.uk
CONTACT:90994
DESCRIPTION:Gene expression in eukaryotes requires synthesis of pre-mRNA b
 y RNA polymerase II (Pol II) and processing to produce mature mRNA. During
  splicing\, introns are removed in a co-transcriptional manner as the nasc
 ent RNA emerges from the Pol II surface. Using cryo-electron microscopy (c
 ryo-EM)\, we determined the structure of a mammalian transcribing Pol II-U
 1 snRNP complex that revealed the molecular basis of a direct interaction 
 between the transcription and splicing machineries. Furthermore\, we ident
 ified that transcription elongation factor SPT6 facilitates the recruitmen
 t of U1 snRNP to elongating Pol II. This multivalent interaction between U
 1 snRNP and the transcription elongation complex may both allow efficient 
 spliceosome assembly and ensure transcription processivity. Beyond co-tran
 scriptional recruitment of splicing factors\, transcription elongation rat
 e also affects co-transcriptional processes\, yet the mechanism of transcr
 iption braking remains unclear. Here we report cryo-EM structures of a DNA
  helicase RECQL5 bound to multiple transcription elongation complexes. Com
 bined with biochemical analysis\, we identify a RECQL5 helix responsible f
 or Pol II interaction and slowdown of transcription elongation. We further
  reveal that the transcription-coupled DNA repair (TCR) complex allows Pol
  II to overcome RECQL5-induced transcription braking. Our results suggest 
 a model in which RECQL5 and the TCR complex coordinately regulate the tran
 scription elongation rate to ensure transcription efficiency while maintai
 ning genome stability.
LOCATION:Jean Thomas Lecture theatre\, Sanger Building\, Tennis Court Road
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