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SUMMARY:Babraham Distinguished Lecture - Different mechanisms define lncRN
 A and protein coding gene transcription units in mammalian cells - Prof. N
 icholas Proudfoot\; Dunn School of Pathology\, University of Oxford
DTSTART:20200123T140000Z
DTEND:20200123T150000Z
UID:TALK127096@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:We have focused on the mechanism of long noncoding (lnc)RNA sy
 nthesis in mammalian cell lines. Many of these lncRNA are associated with 
 protein coding (pc-) genes and include eRNA that derive from pc-gene enhan
 cer regions\, pc-gene promoter associated antisense transcripts\, pc-gene 
 antisense transcripts and separate long intergenic noncoding (linc)RNA. Re
 markably even though lncRNA are transcribed by the same RNA polymerase II 
 (Pol II) transcriptional apparatus\, both the beginning and end of lncRNA 
 transcription units (TUs) appear to use radically different mechanisms. 1)
  We show that lncRNA promoters are often associated with R-loop structures
  generally formed by more abundant pc-gene transcripts. The displaced sing
 le strand DNA acts as a de novo Pol II promoter inducing antisense transcr
 iption from the single stranded DNA region (Tan-Wong et al. Mol. Cell. 201
 9). 2) lncRNA in general are only weakly 3’ end processed by cleavage an
 d polyadenylation activity (normally associated with pc-gene transcripts).
  Instead the Integrator complex appears instrumental in promoting length r
 estricted polyA minus lncRNA (Nojima et al. Mol. Cell. 2018). The conseque
 nce of these non-pc-gene mechanisms to define either end of lncRNA TUs is 
 the likely cause of their rapid degradation before release from the chroma
 tin template (Schlackow et al. Mol. Cell. 2017). Functional lncRNA must ev
 ade this nuclear surveillance mechanism to allow sufficient accumulation t
 o effect particular biological processes. We are developing a new approach
  to sequence full length nascent transcripts with their 5’ ends derived 
 from transcription start sites and 3’ ends within the elongating RNA pol
 ymerase complex. This method is an extension of our original mNET-seq appr
 oach (Nojima et al. Cell. 2015) and vividly reveals by single molecule Nan
 opore sequencing the coupled processing of nascent transcripts.\n \nhttp:/
 /www.proudfootlab.co.uk/
LOCATION:Babraham - The Cambridge Building - The Petersfield Lecture Theat
 re
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