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SUMMARY:Biogenesis and function of circular RNAs (circRNAs). - Dr Sebastia
 n Kadener\, University of Jerusalem
DTSTART:20150430T133000Z
DTEND:20150430T143000Z
UID:TALK58073@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Tight regulation of RNA metabolism is essential for normal bra
 in function. This includes co and post-transcriptional regulation\, which 
 are extremely prevalent in neurons. Recently\, circular RNAs (circRNAs)\, 
 a highly abundant new type of regulatory non-coding RNA have been found ac
 ross the animal kingdom. Two of these RNAs have been shown to act as miRNA
  sponges but no function is known for the thousands of other circRNAs\, in
 dicating the existence of a widespread layer of previously unknown gene re
 gulation.\n\nHere we show that circRNAs are generated co-transcriptionally
 . We demonstrate that circularization and linear splicing compete against 
 each other and that these mechanisms are tissue-specific and conserved fro
 m flies to humans. The second exon of the splicing factor muscleblind (MBL
 /MBNL1) is circularized in flies and humans. This circRNA (circMbl) and it
 s flanking introns contain conserved muscleblind binding sites\, which are
  strongly and specifically bound by MBL. Moreover\, modulation of MBL leve
 ls strongly affects the biosynthesis of circMbl and this effect is depende
 nt on the MBL binding sites. In addition\, we show that circRNAs are highl
 y expressed in the fly brain and their host genes are strongly enriched in
  genes with synaptic functions. By manipulating the levels of specific cir
 cRNAs in the brain we are determining functions of these new types of mole
 cules at the physiological and behavioral levels. Last but not least we sh
 ow that temperature dynamically alters the levels of circRNAs in the fly n
 eural tissue. Our preliminary results indicate that this effect is mediate
 d by editing by the enzyme dADAR. In sum\, here we provide evidence for th
 e mechanisms generating circRNAs and we perform the first systematic scree
 ning for circRNA function.\n\n 
LOCATION:Part II Room\, Department of Genetics
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