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SUMMARY:Studies into the biology of metastatic disease reveals tRNA-derive
 d fragments that suppress cancer progression - Sohail Tavazoie\, The Rocke
 feller University\, New York
DTSTART:20160923T120000Z
DTEND:20160923T130000Z
UID:TALK64097@talks.cam.ac.uk
CONTACT:Kate Davenport
DESCRIPTION:The evolution of a cancer to an aggressive state requires alte
 red expression of a large number of genes. How such expression states are 
 established has been an area of intense investigation. The last decade has
  revealed post-transcriptional regulation of gene-expression by small non-
 coding RNAs to be a major mechanism by which aggressive gene expression st
 ates are established. Our lab has found that modulated expression of tissu
 e-specific microRNAs in diverse cancer types is required for metastatic pr
 ogression to occur. The use of these microRNAs as molecular probes has pro
 vided molecular and cellular insights into the biology of this disease. Du
 ring our studies of metastatic cells\, we have stumbled upon another class
  of small-RNAs that are cleavage products of transfer RNAs. We have identi
 fied a subset of such tRNA-derived fragments (tRFs) as suppressors of meta
 static progression. These fragments are tumorsuppressive molecules that ar
 e generated in normal cells upon hypoxic stress but repressed in aggressiv
 e cells. These tRFs suppress growth by binding to the growth promoting RNA
  binding protein YBX1. The binding of these tRFs to YBX1 reduces YBX1 bind
 ing to its native target transcripts\, which encode oncogenic growth promo
 ting proteins. These transcripts are normally stabilized by YBX1. Their re
 duced binding to YBX1 leads to their degradation. Our findings reveal a pr
 eviously unrecognized RNA regulatory code embedded in tRNAs and their tRF 
 products\, which mediate posttranscriptional gene regulation
LOCATION:CRUK CI Lecture Theatre
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